Abstract: The association between breast feeding and the risk of severe cholera was examined in a case-control study of rural Bangladeshi children under 36 months of age who were studied in 1985-1986 during a field trial of killed oral cholera vaccines. A total of 116 cases who were treated for severe cholera were compared with 464 age-matched community controls without severe cholera. Overall, the odds ratio relating breast feeding to severe cholera (0.30, p less than 0.0001) reflected a 70% reduction in the risk of severe cholera among breast-fed children. The estimated reduction of risk declined with age, but was clearly evident in children up to 30 months of age. Although the association between breast feeding and a reduced risk of severe cholera was not significantly greater in children of mothers who had received cholera vaccine than in children whose mothers had received placebo during the trial, maternal vaccination per se was suggestively associated with a reduced risk of severe cholera in their nonvaccinated children (odds ratio = 0.53, p = 0.05). These results indicate that breast feeding was associated with a substantial reduction of the risk of severe cholera and raise the possibility that vaccination of mothers may provide protection to their young children in endemic settings.

Abstract: To address potential concerns over the release of genetically engineered live bacterial vaccines, we constructed a recombination-deficient derivative of the Vibrio cholerae O1 vaccine strain CVD103 (CVD103RM). Oral immunization of adult volunteers with CVD103RM showed that the recA mutation significantly diminished colonization ability and immunogenicity of the vaccine strain.

Abstract: A questionnaire describing five hypothetical patients intending to travel to different countries was sent to 113 general practitioners, who were asked to state which patients they would recommend cholera vaccination to. The response rate was 80%. The general practitioners' recommendations were compared with those of the Liverpool School of Tropical Medicine. Sixty three of 86 respondents recommended cholera vaccination when it would probably have been unnecessary. A review of common sources of information on cholera vaccination showed that general practitioners are given confusing or inappropriate advice. General practitioners should be educated about when cholera vaccination is necessary; alternatively, the vaccine should be available only through special centres.

Abstract: An oral cholera vaccine consisting of the immunogenic but completely nontoxic B subunit of cholera toxin in combination with heat- and formalin-killed cholera vibrios has been developed. This vaccine, which was designed to evoke antitoxic as well as antibacterial intestinal immunity, has in extensive clinical trials including a large field trial been shown to confer, without any side-effects, protection against cholera lasting for at least 3 years. The vaccine also induced protection of shorter duration against diarrhea caused by enterotoxinogenic Escherichia coli (ETEC). Significant progress has also been made recently using recombinant DNA techniques towards development of a live attenuated oral cholera vaccine. Furthermore, new knowledge about virulence factors and protective antigens of ETEC has given promise that an effective oral ETEC vaccine may soon be developed combining a B subunit toxoid with inactivated ETEC expressing the most important colonization fimbrial antigens.

Abstract: References 1 Cobby M, Higgs CMB, Hall CL. Behcet's syndrome presenting as intracranial hypertension in a Caucasian. J R Soc Med 1988;81:478-9 2 Editorial. Behcet's disease. Lancet 1989;;;761-2 3 Masuda K, Urayama A, Kogure M, Nakajima A, Nakae K, Inaba G. Double-masked trial ofcyclosporin versuscolchicine and long-term openstudy of cyclosporin in Behcet's disease. Lancet 1989;i:l093-6 4 Sultan Y, Kazatchkine MD, Maisonneuve P, Nyddeger UE. Anti-idiotypic suppression of autoantibodies to factor VIII

Abstract: Liposomes were prepared from bovine brain sphingomyelin and cholesterol. They were reinforced by incorporation of osmium tetroxide to prevent their immediate degradation inside the host. Combined Vibrio cholerae antigens (lipopolysaccharide, crude cell·bound hemagglutinin and procholeragenoid) were orally administered to experimental rats either as free or IIposome·associated. A total of 70 experimental rats was utilized in experiments comparing the immune responses of rats to liposome·associated vaccine, free vaccine, liposomes, or placebo, and to vaccines where the lipid or antigen levels were reduced. Immediately after feeding with sodium bicarbonate to lower the gastric acidity, they were fed either cholera vaccines or placebo. Results from serum ELISA revealed that the liposomes localized the immune response to the intestinal mucosa. They displayed an adjuvant property in term~ of evoking a higher immune response to V. cholerae antigens, as measured by the appearance of specific antibody·producing cells in the intestinal mucosa, than when the antigens were fed alone. The adjuvanticity was found to be lipid dose dependent. Liposomes prepared with high lipid content enhanced immuno· genicity of the admixture antigens to a greater degree.

Abstract: One hundred and seventy-one male adults were screened in recruitment of volunteers for a cholera vaccine trial. A full medical history and a physical examination were performed on each subject. The percentages of subjects vaccinated against cholera and typhoid within twelve months were 4 and 1 per cent respectively, while 88 and 15 per cent respectively had been vaccinated more than a year. Biochemical screening revealed abnormal liver function tests in 40.7 per cent, specifically alkaline phosphatase (8%), glutamic oxaloacetic transaminase (8%), glutamic pyruvic transaminase (4.7%), total bilirubin (10%) and globulin (34%). Ten (6%) of the volunteers were positive for hepatitis B surface antigen (HBs-Ag). The total white cell count was elevated in 13.5 and 81.9 per cent had eosinophilia. Stool examination revealed infection with Hookworm (54.9%), Opisthorchis viverrini (29.8%), Strongyloides stercoralis (5.3%), Endolimax nana (3.5%), Giardia lamblia (5.3%) and Taenia saginata (2.9%). Few volunteers (13.4%) had abnormal microscopic examination of urine sediment. Only 57 subjects were considered suitable to be volunteers. Each of these subjects had no significant past medical, surgical or psychological illness. None had been vaccinated against cholera within the previous 12 months and no subject had abnormalities on physical examination or routine biochemical and haematological screening. The large number of subjects excluded from recruitment (67%) emphasized the importance of proper screening of volunteers for any vaccine trial.

Abstract: 121 serum samples from African adults previously immunised with 17 D yellow fever vaccine alone (control group) or simultaneous yellow fever and cholera vaccines were tested for yellow fever antibodies by seroneutralization and haemagglutination inhibition assays. Comparison of the rates of seroconversion and antibody titers between the groups vaccinated the same day or into a short (less than or equal to 10 days) or a long time interval with both vaccines and the control group gave no significant difference. The association of cholera and yellow fever vaccines do not influence the long-term efficiency of yellow fever vaccination.

Abstract: A recombinant plasmid pMM-CTB containing the gene for production of the nontoxic B subunit of Vibrio cholera was transferred into a safe, effective and attenuated oral vaccine Ty21a strain of Salmonella typhi. The resulting Ty21a (pMM-CTB) could steadily produce CT-B subunit that was secreted extracellularly and had the same antigenicity as CT-B produced by V. cholera. Furthermore, the characteristics of the antigenicity, the persistance in mice and the galactose sensitivity possessed in the strain of Ty21a were also retained in Ty21a (pMM-CTB). A bivalent vaccine containing Ty21a (pMM-CTB) and the killed whole cell of V. cholera was then constructed which had good immunogenecity for typhoid fever and cholera diarrhea.

Abstract: 276 volunteers aged 19 years and over were placed under observation in the course of the trial of oral cholera vaccine in tablets, containing choleragen toxoid, O-antigens of serovars Inaba and Ogawa and a number of Vibrio cholerae exoenzymes, for safety, reactogenic properties and immunological effectiveness. The vaccine was found to produce no reactions in a dose of 1-4 tablets; the administration of 3 tablets (300,000 binding units of the toxoid and 10,000 units of O-antigens, serovars Inaba and Ogawa) was shown to induce the most intensive synthesis of both antitoxins and vibriocidal antibodies in the blood sera of volunteers, as well as IgA coproantibodies. The oral vaccine was found to have an advantage over parenteral vaccines due to the absence of reactogenic properties and the formation of local immunity: coproantibodies appeared in 80% and 9% of the vaccinees respectively.

Abstract: PURPOSE:To synthesize a porcine cholera attenuated virus strain by subculturing and acclimating a lapinized porcine cholera attenuated virus LPC-China strain without passing through a primary cultured cell of an animal into an established cell derived from the porcine kidney. CONSTITUTION:A lapinized porcine cholera attenuated virus LPC-China strain is subcultured and acclimated into an established cell derived from the porcine kidney, such as an established cell originating from PK15, without passing through a primary cultured cell of an animal to prepare a porcine cholera attenuated virus strain. The LPC-China strain is preferably obtained by a method for subculturing the China strain with an MPKIIIaCl1 cell which is an established cell derived from the porcine kidney for 10 passages, cloning the established cell PK15 and further subculturing and acclimating the resultant cloned NPK cell for 10 passages. The obtained porcine cholera attenuated virus strain can be used to efficiently produce an excellent porcine cholera vaccine.

Abstract: PIP: Since diarrhea is responsible for considerable morbidity and mortality in India as well as in developing and developed countries, public health specialists strive to develop vaccines against various pathogens which cause diarrhea. Rotavirus (RV) causes 20-40% of severe diarrhea among 6-24 month olds. So they hope for a single dose vaccine against all 4 RV serotypes which can be administered to newborns, but such a vaccine does not yet exist. The bovine and rhesus vaccines are the only heterologous candidate vaccines available, (as of the end of 1989). Another candidate vaccine is the human-animal reassortant RV vaccine where scientists incorporate the VP7 surface protein of human RV into animal RV. The 3rd type of RV candidate vaccine include the naturally attenuated human RV (nursery strains). Vibrio cholerae also causes significant diarrhea in India. Researchers have conducted field trials of many cholera vaccines since the mid 1990s, but they could not find a vaccine which could be used for mass vaccination against cholera. In fact, the cholera vaccine currently used only provides 50% protection, lasts 3-6 months, does not affect carriers, and does not protect against all strains. Salmonella typhi also causes diarrhea, especially among school age children and young adults. The results of large scale field trials in the 1960s reveal that 2 doses of the acetone inactivated typhoid vaccine performed the best of the injectable killed whole cell vaccines. In fact, it provides 79-93% protection and lasts 3-4 years. Further the live oral Ty21a lyophilized vaccine reconstituted in a liquid form and given in multiple doses provides comparable protection (71-96%) against typhoid as well as some protection against paratyphoid. Moreover they induce no side effects. Shigella species also cause diarrhea, especially in children. Various candidate vaccines against shigellosis include the spontaneously attenuated vaccines, streptomycin dependent vaccines, toxoid against exotoxins, and mutant hybrid strains.

Abstract: During the last 10 years, rapid progress in basic research and biotechnology related to enteric infection has now begun to have a substantial impact on vaccine development against these infections. Two new typhoid vaccines, one for oral administration and the other for injection, which have much fewer and milder side effects than previous whole-cell parenteral vaccines, have become available. An oral cholera vaccine has been developed which, without any adverse reactions at all, confers long-lasting protection against cholera. The new cholera vaccine also, through antitoxic immunologic cross-reactivity, protects significantly against diarrhea caused by enterotoxigenic Escherichia coli (ETEC). Notable progress has also been made towards the development of an oral killed vaccine against ETEC diarrhoea as well as live attenuated vaccines against rotaviruses, cholera and shigellosis.

Abstract: Pathogenic strains of Vibrio cholerae O1 elaborate a toxin-coregulated pilus, designated TCP, that is required for the bacteria to colonize the human intestine and cause disease. The possibility that antibodies directed against TCP might block colonization and thereby potentially prevent infection was investigated. The pilus was purified and polyclonal antiserum raised against it was shown to react preferentially with the 20.5-kDa major pilin subunit, TcpA. This antiserum inhibited attachment of the bacteria to epithelial cells in vitro. In a cholera animal model system, these pilus-specific antibodies efficiently protected infant mice from challenge with virulent V. cholerae strains of different serotypes and biotypes. Western immunoblot analysis of available killed, whole-cell vaccine preparations using TcpA-specific antibodies failed to detect pilin in either preparation. The results suggest that inclusion of TCP in cholera vaccines would provide a common antigen to induce immunity to the strains associated with human infection and potentially increase vaccine efficacy.

Abstract: A live oral vaccine consisting of attenuated Salmonella typhi Ty21a expressing Vibrio cholerae O1 Inaba lipopolysaccharide (LPS) O antigen was constructed and tested in volunteers for safety, immunogenicity, and efficacy. Fourteen adults ingested three doses of 10(10) viable organisms with buffer. One month later, 8 vaccinees and 13 unimmunized controls were challenged with 10(6) pathogenic V. cholerae O1 E1 T or Inaba organisms. No significant adverse reactions to vaccination were observed. All volunteers had significant rises in serum immunoglobulin G (IgG) antibody to S. typhi LPS. Only 2 (14%) of 14 had significant rises in serum IgA or IgG antibody to Inaba LPS, and 5 (36%) of 14 had fourfold rises in vibriocidal antibody. In the challenge study, diarrhea occurred in 13 of 13 controls and 6 of 8 vaccinees (vaccine efficacy, 25%; P = 0.13). The vaccine significantly reduced the severity of the clinical illness (P less than 0.05) and caused decreased excretion of challenge vibrios (P less than 0.05). Although the typhoid-cholera hybrid vaccine did not provide significant protection overall against experimental cholera, this study demonstrates the importance of antibody to V. cholerae O antigen in ameliorating clinical illness and illustrates the use of an S. typhi carrier vaccine strain expressing a foreign antigen.