Antibody responses after immunization with killed oral cholera vaccines during the 1985 vaccine field trial in Bangladesh. A serological survey for cholera antibodies in rural east Pakistan. 2. A comparison of antibody titres in the innunized and control populationd of a cholera-vaccine field-trial area and the relation of antibody titre to cholera case rate. Field trial of oral cholera vaccines in Bangladesh: results of one year of follow-up. Comparative study of reactions and serological response to cholera vaccines in a controlled field trial conducted in the USSR. IMPACT OF B SUBUNIT KILLED WHOLE-CELL AND KILLED WHOLE-CELL-ONLY ORAL VACCINES AGAINST CHOLERA UPON TREATED DIARRHOEAL ILLNESS AND MORTALITY IN AN AREA ENDEMIC FOR CHOLERA Safety and immunogenicity of the oral, whole cell/recombinant B subunit cholera vaccine in North American volunteers. A controlled field trial of plain and aluminium hydroxide-adsorbed cholera vaccines in Surabaya, Indonesia, during 1973--75. Protective efficacy in humans of killed whole-vibrio oral cholera vaccine with and without the B subunit of cholera toxin. ABO blood groups and cholera: new observations on specificity of risk and modification of vaccine efficacy. Cholera incidence in a population offered cholera vaccination: comparison of cooperative and uncooperative groups. Cholera vaccine field trials in east Pakistan. 2. Effectiveness in the field. Effects of undernutrition on infection with Vibrio cholerae O1 and on response to oral cholera vaccine. Exclusion of clinically atypical or microbiologically mixed diarrhoeal episodes from outcome events in a field trial of oral cholera vaccines. Safety and immunogenicity of oral killed whole cell recombinant B subunit cholera vaccine in Barranquilla, Colombia. Field trial of oral cholera vaccines in Bangladesh: results from three-year follow-up Field trials of monovalent Ogawa and Inaba cholera vaccines in rural Bangladesh--three years of observation. A serological survey for cholear antibodies in rural east Pakistan. 1. The distribution of antibody in the control population of a cholera-vaccine field-trial area and the relation of antibody titre to the pattern of endemic cholera. Antibody response in the intestinal secretions of volunteers immunized with various cholera vaccines. Report of the 1966-67 cholera vaccine trial in rural East Pakistan. Intestinal and systemic immune responses in humans after oral immunization with a bivalent B subunit-O1/O139 whole cell cholera vaccine. Protective efficacy of oral whole-cell/recombinant-B-subunit cholera vaccine in Peruvian military recruits B subunit-whole cell and whole cell-only oral vaccines against cholera: studies on reactogenicity and immunogenicity. Community-based assessment of safety and immunogenicity of the whole cell plus recombinant B subunit (WC/rBS) oral cholera vaccine in Peru. Impaired immune response to natural infection as a correlate of vaccine failure in a field trial of killed oral cholera vaccines. FIELD TRIAL OF ORAL CHOLERA VACCINES IN BANGLADESH Effect of neutralization of gastric acid on immune responses to an oral B subunit, killed whole-cell cholera vaccine. Field trial of inactivated oral cholera vaccines in Bangladesh: results from 5 years of follow-up. Safety and immunogenicity of an oral recombinant cholera B subunit-whole cell vaccine in Swedish volunteers. Oral cholera vaccines containing B-subunit-killed whole cells and killed whole cells only. II. Field evaluation of cross-protection against other members of the Vibrionaceae family. Intestinal secretory antibody response induced by an oral cholera vaccine in human volunteers. Field trial of oral cholera vaccines in Bangladesh: evaluation of anti-bacterial and anti-toxic breast-milk immunity in response to ingestion of the vaccines. Cross-protection by B subunit-whole cell cholera vaccine against diarrhea associated with heat-labile toxin-producing enterotoxigenic Escherichia coli: results of a large-scale field trial. [Community trial for safety and immunogenicity of oral-administered lyophilized rBS-WC cholera vaccine]. Immunogenicity of two formulations of oral cholera vaccines in Thai volunteers. Cholera vaccine field trials in east Pakistan. 1. Reaction and antigenicity studies. Field trial of oral cholera vaccines in Bangladesh: serum vibriocidal and antitoxic antibodies as markers of the risk of cholera. Report of the 1966-67 cholera vaccine field trial in rural East Pakistan. 2. Results of the serological surveys in the study population--the relationship of case rate to antibody titre and an estimate of the inapparent infection rate with Vibrio cholerae. Immunological response to Vibrio cholerae O1 infection and an oral cholera vaccine among Peruvians. [Initial controlled clinical trials of an oral anticholera vaccine during the cholera epidemic in the district of Malemba-Nkulu (Shaba-Zaire)]. Safety and immunogenicity of an oral, killed enterotoxigenic Escherichia coli-cholera toxin B subunit vaccine in Egyptian adults. Prevention of travellers' diarrhoea by oral B-subunit/whole-cell cholera vaccine Nonparticipation as a determinant of adverse health outcomes in a field trial of oral cholera vaccines. Field trial of a locally produced, killed, oral cholera vaccine in Vietnam Efficacy of vaccination of family contacts of cholera cases. Five-year immunologic memory in Swedish volunteers after oral cholera vaccination.
Sera collected during the 1985 oral cholera vaccine trial in Matlab , Bangladesh , which demonstrated efficacy of a whole cell combined with cholera B subunit vaccine ( WC/BS ) and a whole cell only vaccine ( WC ) , were analyzed for antitoxin and vibriocidal antibodies . Before vaccines were given , antitoxin titers were highest in children , especially those with O blood group , whereas vibriocidal titers rose throughout life . Two weeks after three doses of vaccine , geometric mean antitoxin titers were 2.5 - 4.5 times higher in vaccinees who received the WC/BS vaccine ; the vibriocidal titers were 1.3 - 2.1 times higher in vaccinees who received either vaccine . The titer elevations were relatively brief and were barely detectable 7 months after the third dose even though significant levels of protection persisted greater than or equal to 3 years . Thus , the oral vaccines induced a serum response in this large field trial that was similar to that seen in earlier pilot studies , but the duration of the serum responses was much shorter than the duration of the protection Controlled field trials of a highly antigenic cholera vaccine were held in Matlab Bazar in rural East Pakistan in 1963 and again in 1964 . In July-September 1965 , a serological survey for cholera antibodies was carried out on a r and om sample of the field-trial population . This survey revealed that it was possible to demonstrate the effect of a single injection of the cholera vaccine per head on the proportion of the population with detectable vibriocidal and agglutinating antibody 10 and 22 months after injection . More significantly , the reduction in cholera case rate caused by the vaccine could be correlated with the rise in vibriocidal antibody after vaccination , suggesting that the serological response to vaccine in man may be a useful measure of vaccine potency . The survey also indicated that in this endemic cholera area , with a high level of immunity in adults , a single injection of cholera vaccine was in fact a booster dose for the majority of the population . Thus , the results of cholera vaccine field trials in endemic areas can not be directly extrapolated to predict the effects of the same vaccine in non-endemic areas We assessed the protective efficacy ( PE ) of three doses of B subunit-killed whole cell ( BS-WC ) and killed whole cell-only ( WC ) oral cholera vaccines in a r and omized , double-blind trial among 62,285 children and women residing in rural Bangladesh . After one complete year of surveillance , 110 cases of cholera were detected in the placebo group , 52 in the WC group ( PE , 53 % ; P less than .0001 ) , and 41 in the BS-WC group ( PE , 62 % ; P less than .0001 ) . Protection was greater for BS-WC recipients than for WC recipients only during the initial eight months of observation . Both vaccines conferred equivalent protection against cholera associated with life-threatening dehydration and against less severe cholera . High- grade , sustained protection was observed in persons vaccinated when older than five years ; in younger persons protection was transient . We conclude that BS-WC and WC vaccines confer significant protection against cholera , particularly in persons vaccinated when older than five years This article presents the results of a comparative study of the reactogenicity and the serological response induced by a number of cholera vaccines . Conducted in the USSR on 998 adults aged 18 years and over , the study covered whole-cell heat-killed and formalin-inactivated cholera vaccines , whole-cell heat-killed El Tor vaccine , and a new partially purified toxoid preparation proposed for the immunoprophylaxis of cholera-all administered by hypodermic syringe or jet injector . The most marked reactions were found to occur with the formalin-inactivated cholera vaccine and the least marked with the partially purified toxoid . It was also established that the toxoid was no less effective than the whole-cell vaccine in inducing the intense production of antibodies to the Inaba serotype and , in somewhat lesser degree , to the Ogawa serotype of the El Tor vibrio . It was the only preparation to give rise to intense production of specific antitoxins in 95 - 98 % of cases . The reactions to and immunogenic properties of the  cholera vaccines  did not show any statistically significant difference whether administered by hypodermic syringe or by jet injector The impact of B subunit killed whole-cell ( BS-WC ) and killed whole-cell-only ( WC ) oral cholera vaccines was assessed in a r and omised double-blind trial in rural Bangladesh . 62,285 children aged 2 - 15 years and women aged over 15 ingested three doses of one of the vaccines or placebo . During the first year of follow-up there was a 26 % reduction of all visits for treatment of diarrhoea in the BS-WC group and a 22 % reduction in the WC group . The reduction of all admissions for fatal or severely dehydrating diarrhoea was 48 % in the BS-WC group and 33 % in the WC group . Overall mortality rates were 26 % lower in the BS-WC group and 23 % lower in the WC group during the first year , and reductions of mortality were observed only in women vaccinated at ages over 15 years . However , no differences in cumulative mortality were evident at the end of the second year of surveillance A newly formulated , oral , inactivated whole cell plus recombinant B subunit ( WC/rBS ) cholera vaccine was evaluated in US military personnel . In the first study , 74 subjects were given two doses 14 days apart . In the second study , 186 subjects were r and omized into four groups ; two groups received vaccine with either full ( 4 g ) or half ( 2 g ) strength bicarbonate buffer , and two groups received either full or half strength buffer without vaccine .  Mild gastrointestinal symptoms were associated with full buffer ( P = .02 ) but not with the vaccine . In the first study , 36 % of all subjects and 55 % with low prevaccination titers ( < 1:40 ) had a > or = 2-fold rise in vibriocidal antibody level ; > 80 % of subjects developed a 4-fold rise in anti-cholera toxin ( CT ) titers . Post-vaccination IgA and IgG anti-CT titers were approximately 1.5-fold higher among persons receiving full strength buffer ( P = .05 ) . The WC/rBS vaccine is safe and immunogenic in North Americans , although some mild gastrointestinal symptoms occur with the high concentration of buffer necessary to protect the B subunit from gastric acid denaturation . Prior immunity to cholera conferred by parenteral vaccine decreased vibriocidal antibody response A controlled field trial comparing the effectiveness of a plain cholera vaccine with that of a vaccine adsorbed to aluminium hydroxide was carried out in a cholera-endemic area of Indonesia during 1973 - 75 .  Tetanus toxoid adsorbed to aluminium phosphate was used as the control . In vaccinees aged 1 - 4 years , the adsorbed cholera vaccine provided about 88 % protection for 6 months following vaccination and still provided about 50 % protection between 11 and 14 months after vaccination . In the same age group , the plain vaccine provided only 53 % protection during the first 6 months and no appreciable protection beyond that period . In those aged 5 years and over , both vaccines provided 50 - 60 % protection throughout the period of observation ( 14 months ) . Neither vaccine caused any serious side effects Natural protection from cholera is associated with local intestinal antibacterial and antitoxic antibodies , which appear to act synergistically . Although current parenteral cholera vaccines offer insufficient protection , new vaccines administered orally have more promise . Killed Vibrio cholerae , alone or given with the B subunit of cholera toxin , was evaluated in adult volunteers .  Vaccinees , who received three doses of either vaccine , and unvaccinated controls ingested 10(6 ) V. cholerae organisms to determine the protective efficacy of the vaccines . The combination vaccine provided 64 % protection , and the whole vibrio vaccine given alone provided 56 % protection . In addition , illnesses in vaccines were milder than those in controls , and both vaccines gave complete protection against more severe disease . This substantial level of protection against a dose of V. cholerae that caused cholera in nearly 90 % of controls suggests that these vaccines might provide at least as high a level of protection if given to the population of an endemic area . Indeed , a field efficacy trial is underway in Bangladesh , and preliminary data indicate a protective efficacy of 85 % for a killed whole vibrio plus B subunit vaccine similar to that tested in volunteers and an efficacy of 58 % for the killed whole vibrio vaccine alone . Thus , the studies in human volunteers were successful in predicting the substantial protection afforded by the vaccines in a cholera endemic area La protection notablement plus faible de cholera grave observe chez les receveurs du groupe O de vaccins oraux tues contre le cholera montre bien que les distinctions genetiques peuvent expliquer les variations importantes de l'efficacite des vaccins et que les groupes sanguins ABO doivent etre ajoutes a la liste des sous-groupes epidemiologiques pour l'evaluation de l'efficacite des vaccins dans les futurs essais sur le terrain des vaccins contre le From May 1964 to December 1965 , a controlled field trial of the effectiveness of  cholera and cholera El  Tor  vaccines  was conducted in Negros Occidental , Philippines . Some people did not volunteer for vaccination , and of those who did some received cholera vaccine and others a control ( typhoid ) vaccine . After analysing he incidence of cholera among these three groups it was found that the morbidity and mortality rates were significantly higher in the unvaccinated group than in either the control vaccine group or the cholera vaccine group . This would indicate that the unvaccinated group is basically different from the vaccinated control group . The clinical course of the disease was the same whether the patient had been vaccinated or not . The reasons for non-vaccination were investigated and should be taken into account by public health agencies when immunization programmes are being planned A cholera-vaccine field trial in a rural area of East Pakistan where cholera is highly endemic has indicated that a high-potency whole-cell vaccine can provide significant protection against disease due to Vibrio cholerae for at least 18 months . This vaccine gave more than 70 % protection during the first cholera season after vaccination . In the second cholera season after the administration of a single dose of vaccine , protection fell in those under 5 years of age , while continuing at significantly effective levels in older persons .  Purified Ogawa antigen ( lipopolysaccharide ) afforded significant protection to adults against disease due to the heterologous Inaba serotype , but only protected children against milder diarrhoeas . The effect of cholera vaccine on the incidence of infections among family contacts of cholera patients was variable . Vaccine had no effect on the proportion of asymptomatic infections . Diarrhoeal disease associated with V. cholerae occurred predominantly among children , while protection was most marked among adults . Adverse reactions were practically restricted to the adults , suggesting that children will not only tolerate a larger dose , but actually require a larger dose for maximum protection against infection The association between undernutrition and the risk of colonization and disease with Vibrio cholerae O1 , concentrations of salivary IgA and the serologic response to infection and to orally administered cholera B subunit were examined prospect ively in a family study in Bangladesh . Children ages 1 to 8 years who were family contacts of patients hospitalized with culture-confirmed cholera were visited within 24 hours of the hospitalization and daily for 10 days , queried for the presence of diarrhea and cultured for V. cholerae O1 . On Day 1 each child was weighed and saliva was collected to measure total IgA. On Days 1 and 21 blood was taken to assess vibriocidal and antitoxin titers , and on Days 1 and 2 B subunit or placebo was given orally as part of a trial to look for a toxin-blocking effect . Of 412 children enrolled in the study 35 % ( 143 ) became infected with V. cholerae O1 and 49 % ( 70 ) of these developed diarrhea . Undernutrition , defined in a child as weight less than 70 % of the Harvard reference weight-for-age , was not associated with colonization , disease or the duration or severity of cholera . Moreover well-nourished children did not differ from undernourished children in their concentrations of salivary total IgA , initial serum antitoxin or vibriocidal antibodies or in their serologic response to colonization , disease or B subunit . The immune system in its response to cholera appears to be quite resistant to nutritional insults . The good antitoxin response to B subunit among undernourished children is of particular importance in considering the use of future oral cholera vaccines in areas where such undernutrition is common We investigated whether alternative clinical and microbiological criteria for outcome events affected estimates of vaccine efficacy in a r and omized , double-blind field trial of B subunit-killed whole cell ( BS-WC ) and killed whole cell-only ( WC ) oral cholera vaccines among 62,285 rural Bangladeshi participants . At one year of follow-up estimates of vaccine protective efficacy ( PE = 60 % , P less than 0.0001 for BS-WC ; PE = 54 % , P less than 0.0001 for WC ) against all treated diarrhoeal episodes associated with V. cholerae 01 were similar to estimates of efficacy against only those episodes which were clinical ly typical and unassociated with additional enteric pathogens ( PE = 62 % , P less than 0.0001 for BS-WC ; PE = 52 % , P less than 0.0001 for WC ) . In contrast , estimates of vaccine cross-protection against episodes associated with each of several agents antigenically related to V. cholerae 01 ( LT-ETEC , non-cholera Vibrio sp , Aeromonas sp ) were substantially reduced when mixed infections with V. cholerae 01 were excluded . We conclude that restrictive criteria intended to improve the specificity of the definition of cholera did not increase the detectability of vaccine efficacy against V. cholerae 01 , but that exclusion of mixed infections with V. cholerae 01 was necessary to avoid false-positive conclusions about vaccine cross-protection against other potential target pathogens In January and February 1992 , an assessment was conducted of the safety and immunogenicity of two doses of a new oral cholera vaccine prepared from the recombinant B subunit of the toxin and from killed whole cells ( rBS/WC ) in 1,165 individuals between the ages of 12 months and 64 years in Barranquilla , Colombia . This was a r and omized , double-blind placebo-controlled study . Participants received two doses of either the vaccine or a placebo ( killed Escherichia coli K12 ) over a two-week interval . Few symptoms were detected during the three days following administration of the initial dose and even fewer following the second . Sera obtained upon administration of the first dose and two weeks after administration of the second were tested for Vibrio cholerae 01 Inaba vibriocidal antibodies and antitoxins . Geometric mean titers ( GMT ) of vibriocidal antibodies were found to increase two-fold in subjects receiving the vaccine . In the paired sample s taken from vaccinated subjects , two-fold or greater increases were observed in 44 % and four-fold or greater increases were observed in 34 % , as compared to similar increases in 9.2 % and 2.2 % of the sera taken from those receiving the placebo ( P < 0.05 ) . The GMTs of IgG and IgA antitoxins , as determined by ELISA , increased by factors of 4 and 3.2 , respectively , in those receiving the vaccine , as compared to factors of 1.1 and 1.1 in those given the placebo ( P < 0.001 for IgG , P < 0.01 for IgA ) . Approximately 80 % of the paired sample s from the vaccinated group showed an increase of both IgG and IgA antitoxins > or = 1.5 , as compared to only about 20 % of those in the placebo group ( P < 0.000001 ) . Belonging to the O blood group did not significantly affect the immune response . Children under age four tended to show a weaker vibriocidal antibody response and a stronger antitoxin response than older subjects . The two doses of oral vaccine were found to be safe and without attributable side-effects . The vibriocidal antibody and antitoxin responses were similar to those obtained previously with the conventional oral killed whole cell B subunit cholera vaccine The protective efficacy ( PE ) of B subunit killed whole-cell ( BS-WC ) and killed whole-cell-only ( WC ) oral cholera vaccines was assessed in a r and omised double-blind field trial among children aged 2 - 15 years and women over 15 years in rural Bangladesh . Among the 62 285 subjects who received three doses of  BS-WC , WC , or Escherichia coli K12 strain placebo , cumulative PE at 3 years of follow-up was 50 % for BS-WC and 52 % for WC . PE was similar against severe and non-severe cholera , but was significantly lower in children who were vaccinated at 2 - 5 years ( 26 % for BS-WC ; 23 % for WC ) than in older persons ( 63 % for BS-WC ; 68 % for WC ) . Among persons vaccinated at 2 - 5 years , protection at 4 - 6 months of follow-up was similar to that for older persons , but rapidly waned thereafter and was not evident during the third year of follow-up . In contrast , persons vaccinated at older ages were protected even in the third year of follow-up ( PE 40 % for BS-WC ; 62 % for WC ) . PE was substantially higher against classical cholera ( 58 % for BS-WC ; 60 % for WC ) than against El Tor cholera ( 39 % and 40 % ) A controlled cholera vaccine field trial was carried out to test the efficacy of monovalent whole-cell Inaba and Ogawa cholera vaccines and a purified Inaba antigen . This study was design ed particularly to study the level of protection produced by these vaccines against homologous and heterologous serotypes and to correlate the results with mouse protection tests and human serological response to the vaccines . A cohort of 45 000 children , aged 0 - 14 years , was divided into a control group and three vaccine groups . Inoculations were given annually for 2 years just before the start of the cholera season , and follow-up was continued for one additional year . Essentially , all cholera cases were due to the Inaba serotype , so that protection could be studied only against that serotype . Two annual injections of the whole-cell Inaba vaccine gave the highest level of protection , averaging 84 % over the 3 years of follow-up ; a single injection of the purified Inaba vaccine gave less protection ( 51 % ) . Two annual injections of the whole-cell Ogawa vaccine failed to protect  children under the age of 5 but did produce 48 % protection for children aged 5 - 14 against Inaba cholera . Serological surveys correlated poorly with protection ; specifically , the Ogawa vaccine produced high anti-Inaba titres in young children but no protection . The cross-protection against Inaba cholera produced by Ogawa vaccine in the older children is assumed to be due to boosting of naturally acquired immunity in this population . Monovalent vaccine can not be recommended for general public health use because of the serotype specificity of protection that this study has demonstrated Controlled cholera vaccine field trials were held in Matlab Bazar in rural East Pakistan in 1963 and 1964 . In July-September 1965 , a serological survey for cholera antibodies was carried out on a r and om sample of the field-trial population . Results are given for the control group only , as representative of the pattern found in an endemic cholera area . Only 2 % of the blood sample s from children under 10 years of age were found to have detectable agglutinating antibody ( titres of 1:20 or more ) , while the proportion in the age-group over 30 years was 27%-30 % . Tests for vibriocidal antibody showed that none of the blood sample s from children under 1 year of age contained detectable antibody , while 87%-90 % of those from adults over 30 years did so . The rise in the geometric mean vibriocidal titre showed an almost linear correlation with a sharp fall in the cholera case rate with age . Since a similar survey in a non-endemic area ( Czechoslovakia ) did not reveal any rise in antibody titre with age , and since cholera epidemics in areas without recent experience of the disease are characterized by a higher incidence rate in adults than in children , it is suggested that the antibody titres give a measure of the level of immunity in a population The efficacy of various cholera vaccines in eliciting an intestinal antibody response was assessed in human volunteers who received oral live , oral killed , or parenteral cholera vaccines , or placebo .  The intestinal immune response in terms of antibacterial and antitoxin antibodies was determined 2 and 4 weeks after immunization . By means of the mouse peritoneum opsonization assay and the infant mouse protection test , antibacterial activity could be detected in the intestinal secretions of volunteers who had been immunized either orally or by the parenteral route . Significant protective activity and duration of immunity were observed with the oral killed vaccine . The bacteriological data indicated the absence of significant intestinal colonization of the live attenuated strain after oral administration , and probably explains the observed lack of effectiveness of the oral vaccine compared with that of the killed vaccine . The predominant immunoglobulin class of intestinal antibody was found to be IgA. None of the vaccines used in the study elicited significant antitoxin activity in the intestinal secretions , as determined by the skin permeability neutralization test A controlled cholera vaccine field trial was carried out in rural East Pakistan to determine the efficacy of a cholera vaccine of average antigenic potency when used in a continuing programme with annual reimmunizations . A cohort of 40 000 children aged 0 - 14 years was equally divided into a control group and 3  vaccine groups . Inoculations of vaccine were given annually for 3 years just before the start of the cholera season , and follow-up continued for 2 additional years . The results indicate that there was increasing protection with reimmunization , reaching a maximum with 3 doses . One dose produced 43 % protection , 2 doses 64 % , 3 doses 81 % , and 4 doses 76 % . Protection was more sustained after reimmunization ; being 50 % and 39 % , 1 and 2 years after the fourth injection , respectively . Serological surveys suggested a general parallel in the antibody response to vaccine and the level of protection achieved ; however , the levels of vibriocidal antibody titres could not be related directly to levels of protection . The overall protection achieved with the 3-year programme of annual reimmunizations was 55 % for the group receiving one inoculation annually , and 65 % for the group receiving 2 inoculations in the first year followed by annual reimmunizations . When the costs and effectiveness of annual vaccine programmes are compared with those for cholera treatment centres , it becomes clear that the cholera vaccines now available are not appropriate alternatives to treatment in routine cholera control programmes There is a need for an effective vaccine that can protect against cholera caused by either Vibrio cholerae O1 or by the new p and emic serotype O139 Bengal . An oral bivalent B subunit-O1/O139 whole cell ( B-O1/O139 WC ) cholera vaccine has been prepared by adding formalin-killed O139 vibrios to the recently licensed oral recombinant B-O1 WC vaccine . When tested in Swedish volunteers , this B-O1/O139 WC vaccine was found to be safe and immunogenic . Two vaccine doses given 2 weeks apart induced statistically significant , P < 0.05 , mucosal IgA antibody responses in intestinal lavage fluid against cholera toxin in all of nine vaccinees and against both O1 and O139 vibrios in seven of nine cases . The intestinal responses were associated with similar high frequencies of intestine-derived antibody-secreting cell responses in peripheral blood to the different antigens . A third dose of vaccine given after 5 - 6 weeks did not result in any further increased response . All of 12 vaccinees responded with significant IgA and IgG antitoxin responses in serum associated with significant vibriocidal antibody titre rises against O1 vibrios in 10 cases ( 83 % ) and against O139 vibrios in eight vaccinees ( 67 % ) . The frequencies and magnitudes of the serological responses to the B subunit and O1 WC components were similar to those induced by the B-O1 WC vaccine . Thus , the O139 component of the vaccine induced intestinal and systemic antibacterial immune responses in the majority of the vaccinees , and its addition to the vaccine did not interfere with the immunogenicity of the B subunit or O1 WC components The cholera epidemic in South America has reinforced the need for safe and effective oral vaccines . In a r and omised , double-blind , placebo-controlled efficacy trial among 1563 Peruvian military recruits we have investigated the protective efficacy of an oral inactivated whole-cell/recombinant-B-subunit ( WC/rBS ) cholera vaccine .  Participants were given two oral doses of cholera vaccine or Escherichia coli K12 placebo , with an interval of 7 - 14 days . 1426 ( 91 % ) subjects received the two prescribed doses and were followed up for a mean of 18 weeks ( median 21 weeks ) . After vaccination , Vibrio cholerae O1 El Tor Ogawa was isolated from 17 subjects with diarrhoea . 16 of the cholera cases occurred 2 weeks or longer after the second dose of vaccine ( 14 placebo recipients , 2 vaccinees ) . We also detected 14 symptomless infections ( 11 [ 7 placebo recipients , 4 vaccinees ] ) 2 weeks or longer after the second dose . The vaccine had significant protective efficacy against cholera ( 86 % [ 95 % CI 37 - 97 ] , p < 0.01 ) but not against symptomless infection ( 42 % [ -96 to 85 ] ) . All cholera cases were in people of blood group O , who made up 76 % of the study population ( p < 0.01 ) . Two doses of WC/rBS vaccine , given 1 to 2 weeks apart , provide rapid , short-term protection against symptomatic cholera in adult South Americans , who are predominantly of blood group O. Long-term efficacy studies in Peruvian adults and children are under way We conducted a r and omized trial among persons in rural Bangladesh to evaluate the side effects and immunogenicity of orally administered B subunit-killed whole cell ( BS-WC ) and killed whole cell-only ( WC ) cholera vaccines and a killed Escherichia coli strain K12 placebo proposed for field testing . Three doses of BS-WC , WC , E. coli , or a control agent were given with antacid to 1,257 women ( aged greater than 15 years ) and children ( aged to to 15 years ) . The four groups exhibited no statistically significant differences in occurrence of symptoms after each dose , and rises in titers of vibriocidal ( VC ) antibodies to Inaba and Ogawa were twofold higher for vaccinees than for controls ( P less than .001 ) . Half of the persons with fourfold or greater VC responses to WC responded after the first dose ; many additional patients , particularly young children , responded after subsequent doses . In contrast , 89 % of persons who responded to BS-WC with twofold or greater rises in titer of IgG antibodies to cholera toxin did so after the first dose . After the third dose , vaccinees exhibited a fivefold higher rise in titer than did controls ( P less than .001 ) ; a dose-to-dose booster effect was most evident in young children Every year since its introduction in 1991 , there have been epidemics of cholera in Lima , Peru . Vaccination is one approach to the control of cholera . A pilot study was conducted to assess the safety and immunogenicity of a whole cell plus recombinant B subunit ( WC/rBS ) cholrea vaccine in Lima , Peru . Five hundred and forty-one volunteers aged 2 - 65 years received two doses two weeks apart of WC/rBS vaccine or Escherichia coli K12 placebo administered in bicarbonate buffered water . Symptoms were monitored on all subjects and blood was collected from 102 persons before the first dose and two weeks after the second dose .  Mild post-vaccination gastrointestinal symptoms were reported with equal frequency for both the vaccine and placebo recipients . Among 51 vaccines , 49 % had a twofold or greater increase in serum vibriocidal titers ( GMT = 78 ; range < 1:10 to 1:5120 ) ; and 92 % and 82 % developed a twofold or greater serum anti-cholera toxin IgG and IgA response , respectively . Persons with elevated prevaccination vibriocidal titers had a decreased response to the WC/rBS . Age and blood group did not affect the immune response . The WC/rBS vaccine was safe and immunogenic in a group of native Peruvians In a field trial carried out in 1985 in Matlab , Bangladesh , the authors evaluated whether subjects who developed Vibrio cholerae 01 infections during the first year after earlier receipt of B subunit-killed whole cell ( BS-WC ) or killed whole cell-only ( WC ) oral cholera vaccines  exhibited deficient serum vibriocidal immune responses to these infections . After severe V. cholerae 01 infections ( n = 70 ) in subjects > 5 years of age , the age group in which both vaccines were efficacious , a 6.5 geometric mean-fold rise of serum vibriocidal antibodies was observed among vaccinees , compared with an 18.6 geometric mean-fold rise in placebo-recipients ( p < 0.01 ) . Depressions of serum vibriocidal responses among vaccinees were even more marked after asymptomatic infections ( n = 30 ) : a 1.1 geometric mean-fold rise in vaccinees versus a 5.9 geometric mean-fold rise in placebo-recipients ( p < 0.01 ) . The authors conclude that subjects who failed to be protected by BS-WC and WC , despite being in the age group for which these vaccines were protective , exhibited poor immune responses even to the vigorous stimulus of natural infection . These findings raise the possibility that immune hyporesponsiveness may limit the potential efficacy attainable by cholera vaccines in population s with endemic cholera The protective efficacy of oral B subunit killed whole-cell ( BS-WC ) and killed whole-cell ( WC ) cholera vaccines was assessed in 63 498 Bangladeshi children aged 2 - 15 years and women aged over 15 years . Each received three doses of BS-WC , WC , or placebo in a r and omised , double-blinded fashion . Surveillance for cases seeking medical care up to six months after the third dose revealed 26 cases of confirmed cholera in the placebo group , 4 cases in the BS-WC group ( protective efficacy 85 % ; p less than 0.0001 ) , and 11 cases in the WC group ( protective efficacy 58 % ; p less than 0.01 ) . For each vaccine protective efficacy was consistent in different age-groups ( 2 - 10 years versus greater than 10 years ) and for different severities of cholera Les auteurs rapportent les result ats d'experiences dans lesquelles on verifie si l'exposition a des solutions de faible pH reduit l'activite de la sous-unite β de la toxine cholerique . Les auteurs decrivent egalement une evaluation serologique chez des volontaires humains chez lesquels on teste si le tamponnage par l'acide gastrique affecte les taux d'anticorps contre la toxine cholerique et la reponse en anticorps vibrioacides au vaccin oral To determine the protective efficacy ( PE ) of three doses of oral B subunit-killed whole cell ( BS-WC ) or killed whole cell-only ( WC ) vaccines against cholera , a clinical trial was conducted among 62285 children over 2 years and adult women in rural Bangladesh . During 5 years of follow-up , there were 144 cases of cholera in the BS-WC group ( PE = 49 % ; P < 0.001 ) , 150 in the WC group ( PE = 47 % ; P < 0.001 ) , and 283 in the K12 group . Protection by each vaccine was evident only during the first three years of follow-up ; long-term protection of young children was observed only against classical but not El Tor cholera ; 3-year protection against both cholera biotypes occurred among older persons , but at a higher level against classical cholera The safety and immunogenicity of a ' new ' oral B subunit-whole cell ( B-WC ) cholera vaccine based on recombinantly produced B subunit was evaluated in Swedish volunteers . The recombinant B-WC vaccine was comparable to the ' old ' type of B-WC vaccine in inducing IgA and IgG antitoxin antibody responses as well as vibriocidal antibody responses in serum , which are known to be good serological correlates of the gut mucosal IgA antitoxic and antibacterial immune responses after oral immunization with B-WC vaccine . Neither of the two B-WC vaccines was associated with any significant side-effects . The results indicate that the more easily and cheaply produced recombinant B subunit can replace the ' old ' type of B subunit isolated from cholera toxin for use in the oral B-WC cholera vaccine Because of demonstrable cross-reactivity of cellular antigens contained in B subunit-killed whole-cell ( BS-WC ) and killed whole-cell-only ( WC ) oral cholera vaccines with antigens of various non-cholera species of the family Vibrionaceae ( NCV ) , the protection conferred by the vaccines against diarrhoea associated with NCV was evaluated during a r and omized , double-blind field trial in Bangladesh . Children aged 2 - 15 years and women aged greater than 15 years ( 62,285 in number ) received three doses of BS-WC vaccine , WC-only vaccine , or a placebo consisting of Escherichia coli K12 strain ( K12 ) . During 1 year of follow-up , the incidence of treated episodes of diarrhoea associated with non-cholera vibrios known to be enteric pathogens ( non-01 Vibrio cholerae , V. fluvialis , V. parahaemolyticus , V. mimicus ) in the placebo group was low ( 1.9 cases per 10,000 recipients ) and identical to that for the two vaccine groups combined . The incidence ( per 10,000 recipients ) of treated diarrhoeal episodes associated with Aeromonas species was considerably higher , but nearly identical in the three groups ( 26.1 cases for BS-WC , 26.0 cases for WC ; 25.9 cases for K12 ) . Pleisiomonas shigelloides was not isolated from any participant . It is concluded that NCV other than Aeromonas were rarely isolated from diarrhoeal patients in our study population and that killed oral vaccines which were effective against cholera exhibited no detectable cross-protection against diarrhoea associated with NCV organisms The ability is reported of a new oral cholera vaccine composed of Vibrio cholerae antigenic fractions to induce a serum and mucosal antibody response after three oral administrations of microgranules to 18 French volunteers according to different protocol s of immunization . Specific antibodies were detected in the three different fluids studied ( saliva , jejunal fluid , serum ) in one third of volunteers before vaccination . An increase of specific IgA antibody level was observed in jejunal fluids of most volunteers after oral vaccination . An augmentation of specific antibodies against vaccine antigenic components was also observed in serum and in saliva after vaccination but in fewer volunteers In a field trial conducted in Bangladesh , ingestion of either B subunit-killed whole cell ( BS-WC ) or killed whole cell ( WC ) oral cholera vaccines by mothers was associated with a 47 % reduction of the risk of cholera in their non-vaccinated children aged under 36 months . Because vaccine-induced breast-milk immunity seemed a possible explanation for these findings , we evaluated anti-lipopolysaccharide ( LPS ) and anti-cholera toxin ( CT ) IgA antibody responses in breast milk collected during the trial from 53 lactating women who ingested three doses of BS-WC , WC , or an Escherichia coli K12 strain ( K12 ) . Despite induction of moderate vibriocidal ( 1.4 to 2.0-fold ) and anti-CT ( 4.5-fold ) serum antibody responses , the vaccines did not elicit significant rises of anti-LPS or anti-CT IgA breast-milk antibodies . The failure of the vaccines to elicit significant levels of breast-milk anti-cholera antibodies suggests an alternative explanation for protection of young children by maternal vaccination , such as interruption of maternal-child transmission of Vibrio cholerae 01 The B subunit ( BS ) of cholera toxin and that of the heat-labile enterotoxin ( LT ) of enterotoxigenic Escherichia coli ( ETEC ) are antigenically similar . We therefore assessed whether a combined cholera toxin BS/whole-cell ( BS-WC ) oral vaccine against cholera conferred cross-protection against LT-producing ETEC ( LT-ETEC ) diarrhea in a r and omized , double-blind field trial among rural Bangladeshi children and women . The 24,770 persons who ingested two or more doses of BS-WC vaccine  were compared with 24,842 controls who took two or more doses of killed whole-cell ( WC ) oral cholera vaccine .  Sixty-seven percent fewer episodes of LT-ETEC diarrhea were noted in the BS-WC group than in the WC group during short-term ( three-month ) follow-up ( P less than .01 ) , but no reduction was evident during the ensuing nine months . Short-term protection was particularly notable against LT-ETEC diarrhea causing life-threatening dehydration ( protective efficacy , 86 % ; P less than .05 ) In order to evaluate the safety and immunogenicity of domestic produced lyophilized recombinant , B-subunit , inactivated whole cell vaccine of vibrio cholerae ( rBS-WC ) , 369 subjects were r and omly divided into three groups and observed with masking method , one with high dose of vaccine ( 5 mg rBS and 10 " WC ) , another with low dose ( 1 mg rBS and 10 " WC ) , and the control one with placebo . Three doses of vaccine were given orally at an interval of seven days and 14 days , respectively . Results showed that only one subject had mild adverse reaction in the vaccine group ( 1/247 ) and none in the control group . Serum and fecal antibody conversion rates and average levels of antibodies in the two vaccine groups were significantly higher than those in control one . There was no significant difference in serum and fecal antibody conversion rate and average antibody levels between the two vaccine groups . But , antibody response was different among subjects of various sex , age , and vaccine doses . It indicates that rBS-WC vaccine of vibrio cholerae had good immunogenicity and safety A formulation of oral vaccine consisting of Vibrio cholerae lipopolysaccharides ( LPS ) , cell-bound haemagglutinin ( CHA ) and procholeragenoid ( P ) , namely vaccine A , was compared with another formulation , vaccine B , prepared from killed whole vibrios plus procholeragenoid on their immunogenicity and reactogenicity in Thai male volunteers . Volunteers were r and omly allocated into three groups . The first two groups received orally three doses of vaccines A and B , respectively at 14-day intervals . Volunteers in group 3 were controls and received orally 100 ml 5 % ( w/v ) NaHCO3 also at 14-day intervals . Serum sample s were collected from all volunteers before each immunization . Intestinal lavage was performed 3 to 7 days before the first dose of vaccine or placebo and 7 , 21 and 45 days after the last dose . Serum vibriocidal antibodies were determined and class-specific , antigen-specific antibodies of all serum and lavage sample s were assessed by indirect enzyme-linked immunosorbent assay ( ELISA ) using purified LPS , CHA and cholera toxin ( CT ) as antigens . Diarrhoea occurred in 10 and 40 % of the vaccinees ingesting the vaccines A and B , respectively . The immunogenicity of the vaccine B in terms of seroconversion for vibriocidal antibodies and anti-LPS was higher than the vaccine A. Both vaccines had equal immunogenicity concerning serum anti-CT , while the vaccine A was slightly better than the vaccine B on serum anti-CHA response . The immunogenicity of the two vaccines in evoking intestinal responses was different from the systemic one . ( ABSTRACT TRUNCATED AT 250 WORDS Double-blind controlled  cholera-vaccine trials were carried out in rural East Pakistan in 1963 and 1964 . Pretrial studies indicated that a whole-cell cholera vaccine of high mouse protective potency , at a dose of 0.5 ml , produced an antibody response and reaction pattern consistent with use in such trials . A purified Ogawa antigen , given at a dose of 100 mug , elicited no adverse reactions and evoked both agglutinating and vibriocidal antibodies against both Inaba and Ogawa test suspensions . In the field , adverse reactions to the cholera vaccines occurred primarily among adults and were observed with both the whole-cell preparation and the purified Ogawa antigen . At the dose used in the field trials ( 0.4 ml ) , the reactions elicited by the whole-cell vaccine were acceptable to the population and no more marked than those following the locally prepared typhoid-paratyphoid vaccine .  Delayed reactions to the whole-cell cholera vaccine were observed beginning 4 to 7 days after the vaccine was administered ; the bulk of them ( 60 % ) did not interfere with work at any time ; all resolved promptly ; and none developed fluctuation or was associated with abscess formation The relationship of serum vibriocidal ( VC ) and IgG anti-cholera toxin ( CT ) antibodies to the risk of cholera was evaluated during the first year of follow-up of recipients of three oral doses of B subunit (BS)-whole-cell vaccine , whole-cell vaccine , or Escherichia coli K12 strain placebo in Bangladesh . Acute sera from 121 cholera patients were compared with sera from 2592 contemporaneous community controls . Each doubling of VC titer was associated , on average , with a 22%-47 % reduction of cholera risk in the three groups . In contrast , in the two groups that did not receive BS , anti-CT titers were directly associated with cholera and thus served as markers of higher cholera risk . Each vaccine conferred approximately 65 % protective efficacy against cholera , but antibody titers did not correlate with vaccine efficacy , indicating that serum VC and anti-CT antibodies are poor markers of the longitudinal pattern of vaccine efficacy The 1966 - 67 cholera vaccine field trials in East Pakistan tested 1- and 2-dose schedules of a commercial cholera vaccine in 40 000 children aged 3 months to 14 years . R and om sample serological surveys , made prior to the inoculations and 3 months and 6 months after the inoculations , demonstrated that there was a rise in the vibriocidal titres of the vaccinated children during the first 3 months after inoculation and a subsequent fall by the end of the second 3 months . The antibody response to 2 doses of cholera vaccine was better than the response to a single dose in children under 5 years of age . In children aged 5 - 14 years , the antibody response was similar for both inoculation schedules . Since the majority of the older children had vibriocidal antibodies before inoculation , the data suggest that the single dose acted as a booster , and this effect was not enhanced by a second inoculation . Serological studies of the hospitalized cholera patients indicated that the majority had low vibriocidal titres on admission to hospital . By comparing the distribution of admission titres of the hospitalized patients with the distribution of titres found in the population survey , it was possible to demonstrate a progressive reduction in the cholera case rate for the population with high levels of vibriocidal antibody . The sample surveys from the control population revealed a rise in titre following the peak of the cholera season , and a fall 3 months later . The data suggest that the rate of infection with V. cholerae for the 10 000 children in the control group during the cholera season may have been as high as 27 % , while the clinical case rate was only 0.26 % A ' double-blind ' , r and omized , placebo controlled study of an oral inactivated whole cell plus recombinant B subunit ( WC/rBS ) cholera vaccine was conducted during February-March 1992 in Peru in 346 military recruits , 307 ( 89 % ) of whom received 2 oral doses of vaccine or Escherichia coli K12 placebo , 2 weeks apart . Paired serum sample s were obtained from 155 ( 50 % ) of the recipients of 2 doses . An epidemic of cholera took place between doses . No difference in cholera attack rates was detected between vaccine and placebo recipients after one dose ( 8 % versus 14 % ) . Seroconversion ( 4-fold or higher increase in vibriocidal antibody titres ) was detected in 90 % and 80 % of vaccine and placebo recipients , respectively , with low pre-existing vibriocidal titres ( < 0.01 ) . The anti-cholera toxin seroconversion rate among those with low pre-existing titres was higher in vaccinated subjects ( 97 % ) than in placebo recipients ( 68 % ) ( P < 0.01 ) . Administration of 2 doses of WC/rBS vaccine concomitantly with natural V. cholerae O1 infection enhanced the serum anti-cholera toxin response . The immune response to the whole cell component of the vaccine was reduced by high pre-existing vibriocidal antibody titres The authors have utilized the Institut Pasteur anticholeric vaccine by oral passage amid the Malemba - Nkulu area population . The choleric epidemic beginning six months after the vaccine oral passage . The results had been 67 cholera case on 18,377 subjects non inoculated 25 case on 6,249 subjects inoculated by inject vaccine , 3 case on 12,014 subjects inoculated by vaccine oral passage Enterotoxigenic Escherichia coli ( ETEC ) is the leading cause of bacterial diarrhea in young children in developing countries . The safety and immunogenicity of a killed , oral ETEC vaccine consisting of whole cells plus recombinantly produced cholera toxin B subunit ( rCT B ) was evaluated in Egypt , which is endemic for ETEC diarrhea . Seventy-four healthy Egyptian adults ( 21 - 45 years old ) were r and omized and received two doses of the ETEC/ rCT B vaccine ( E003 ) or placebo 2 weeks apart . The frequency of adverse events after either dose did not differ by treatment group , and no severe adverse events were reported . After vaccination , peripheral blood IgA B cell responses to CTB ( 100 % ) and to vaccine colonization factor antigens CFA/I ( 94 % ) , CS4 ( 100 % ) , CS2 ( 81 % ) , and CS1 ( 69 % ) were significantly higher than response rates for the placebo group . These favorable results in Egyptian adults indicate that the ETEC/ rCT B vaccine is a promising c and i date for evaluation in younger age groups in this setting B-subunit/whole-cell cholera vaccine ( BS-WC ) has been shown to give Bangladeshi mothers and children only 3 months ' protection against severe diarrhoea due to enterotoxigenic Escherichia coli ( ETEC ) . Since a long-lasting effect is not necessary for protection against travellers ' diarrhoea , a prospect i ve double-blind study was conducted among tourists who went to Morocco from Finl and . 307 tourists received two oral doses of BS-WC , whereas 308 controls received a placebo before departure . A research team went out with tourists and a laboratory for enteric pathogens was set up on location . A faecal specimen was taken from 100 r and omly selected subjects before departure , from all travellers with diarrhoea , and routinely after return . Enteropathogenic bacteria were not isolated from any of the pre-departure specimens but were present during or after the holiday in 47 % of tourists with travellers ' diarrhoea , and in 14 % of those without diarrhoea . BS-WC induced a 52 % protection ( p = 0.013 ) against diarrhoea caused by ETEC . The protection was better for mixed infections ( 65 % , p = 0.016 ) . The protective efficacy against a combination of ETEC and any other pathogen was 71 % ( p = 0.02 ) , and that against ETEC plus Salmonella enterica even better at 82 % ( p = 0.01 ) . Partial protection against travellers ' diarrhoea is thus obtainable by active immunisation with BS-WC The authors estimated the incidence rates of cholera and death between 1985 and 1988 for 32,642 age- and sex-eligible persons who did not participate in a r and omized , placebo-controlled field trial of killed oral cholera vaccines in rural Bangladesh . As compared with 20,744 placebo recipients , the relative risk of cholera for all non participants , adjusted for potentially confounding demographic variables , was 1.20 ( 95 % confidence interval ( CI ) 1.03 - 1.41 ) ; this adjusted relative risk reflected elevated adjusted relative risks in non participants who were medically ineligible ( RR = 1.65 ; 95 % CI 1.22 - 2.22 ) or refused to participate ( RR = 1.19 ; 95 % CI 1.01 - 1.41 ) , but not in persons absent at the time of vaccination ( RR = 1.00 ; 95 % CI 0.78 - 1.28 ) . The adjusted relative risk of death was also elevated in non participants as compared with placebo recipients ( RR = 1.28 ; 95 % CI 1.10 - 1.48 ) , with the same pattern of adjusted relative risks for different categories of non participants : for ineligible subjects , 2.64 ( 95 % CI 2.12 - 3.29 ) ; for refusers , 1.20 ( 95 % CI 1.02 - 1.41 ) ; and for absentees , 0.95 ( 95 % CI 0.75 - 1.22 ) . The authors concluded that nonparticipation was associated with clinical ly cogent adverse health outcomes , but that the magnitude of these associations varied according to the reason for nonparticipation . These findings underscore the caution required in assessing vaccine efficacy with controls who are not vaccinated because of choices made by patients or vaccinators BACKGROUND Several studies have shown that orally administered killed cholera vaccines are safe and protective in population s at risk of cholera in developing countries . However , these vaccines have not been adopted for use in developing countries because of their expense and limited efficacy in young children . We have tested an inexpensive , killed whole-cell cholera vaccine developed and produced in Vietnam . METHODS The efficacy of the vaccine was assessed in a large-scale , open field trial in people at least 1 year old residing in 22,653 households in the central coastal city of Hue . Alternate households were assigned vaccine ( 67,395 people ; two doses per person ) or no vaccine ( 67,058 people ) . Surveillance for cholera was conducted in all Ministry of Health facilities serving this population . Analysis was by intention to treat . FINDINGS During an outbreak of El Tor cholera 8 - 10 months after vaccination , 37 cases of cholera requiring inpatient care occurred among age-eligible people allocated to the vaccine group , and 92 cases among age-eligible people allocated to the no-vaccine group ( protective impact 60 % [ 95 % CI 40 - 73 ] ) . Among the 51,975 people who received the complete two-dose vaccine regimen , the protective efficacy was 66 % ( 46 - 79 ) : in this subset , the protective efficacy was similar for children aged 1 - 5 years ( 68 % ) and for older people ( 66 % ) . INTERPRETATION These findings suggest that oral killed whole-cell vaccines can confer substantial protection against El Tor cholera in young children , who are at highest risk of cholera in endemic setting s. An inexpensive , locally produced , and effective oral cholera vaccine may be within reach of the limited health-care budgets of poor countries with endemic cholera , if our findings can be replicated in a r and omised double-blind trial Abstract 742 family contacts of 149 cholera patients with bacteriologically confirmed Vibrio cholerœ Inaba infection were given either placebo ( vaccine diluent ) or monovalent Inaba vaccine of proven efficacy within 12 hours of hospital admission of the index case . Rectal swabs and histories of diarrhœa obtained daily for 10 consecutive days revealed no appreciable difference in subsequent rates of infection , date of onset of positive stools , duration of vibrio shedding , or clinical expression of the disease . Although protection did seem to begin by the 9th day of observation , the numbers were too small to be statistically significant . Given the close temporal clustering of secondary infections among family contacts near the onset of the index case ( well over 95 % had occurred by day 8) , tetracycline remains the prophylactic agent of choice Les result ats montrent que le cholera confere une forte immunoprotection contre de nouveaux acces de la maladie pendant plusieurs annees . Par contre la reponse humorale intestinale a la toxine cholerique et a la bacterie semble ne persister que quelques
BACKGROUND Oral cholera vaccines ( either killed whole cell or live recombinant vaccines ) are newer alternatives to the parenteral vaccines which have been thought to confer only moderate and short-term immunity .
OBJECTIVES The objective of this review was to assess the effect of cholera vaccines in preventing cases of cholera and preventing deaths .