human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 
    Output:
    