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: A r and omized , double-blind trial comparing a diphtheria-tetanus-acellular pertussis vaccine ( DTaP ) ( pertussis toxoid and filamentous hemagglutinin ) with a whole-cell vaccine ( DTwP ) was conducted . A case-contact study was nested in the trial to estimate absolute efficacy . From 1990 through 1994 , 4181 children were r and omized to receive one of the vaccines at 2 , 4 , and 6 months .  Severe adverse events were monitored weekly during two visits after vaccination . Fewer serious adverse events were observed after DTaP. Surveillance for cough illnesses persisting more than 7 days , in children under 15 years of age , was made by weekly home visits . Examining physicians , blind to vaccination status , took sample s for culture and serologic testing . Pertussis was defined as 21 or more days of cough confirmed by culture , serology , or contact with a culture-confirmed person . Beginning 28 days after the third vaccine dose , the overall ratio of pertussis incidence in the DTaP group relative to the DTwP group ( RRac/wc ) was 1.54 ( 95 % CI , 1.23 - 1.93 ) . In children younger than 18 months of age , RRac/wc was 1.16 ( 95 % CI , 0.77 - 1.73 ) and 1.76 ( 95 % CI , 1.33 - 2.33 ) in children older than 18 months , which suggests a shorter duration of protection with the acellular vaccine ( P = 0.090 ) . Absolute efficacy estimates derived from the case-contact study confirmed the lower protection afforded by the acellular vaccine compared with the whole-cell vaccine : 31 % ( 95 % CI , 7 - 49 ) versus 55 % against the protocol case definition , and 85 % ( 95 % CI , 66 - 93 ) versus 96 % for the more severe WHO case definition . Although vaccination with DTaP provided a lower degree of protection than the highly effective DTwP , this difference was less prominent before 18 months of age , the customary age for a fourth dose . The safer DTaP vaccine may prove a valuable substitute for whole-cell vaccines when used in a schedule that includes a booster-dose BACKGROUND In 1992 - 1993 , a r and omized , double-blind , placebo-controlled clinical trial of two 3-component acellular pertussis vaccines was started in 4 of Italy 's 20 regions . During the trial , the children had been r and omized to receive 3 doses of 1 of 2 acellular pertussis vaccines combined with diphtheria and tetanus toxoids ( DT ) or of a DT vaccine only , at 2 , 4 , and 6 months of age . Both diphtheria-tetanus-acellular pertussis ( DTaP ) vaccines , 1 manufactured by SmithKline Beecham ( DTaP SB ; Infanrix ) and 1 manufactured by Chiron Biocine ( DTaP CB ; Triacelluvax ) , contain pertussis toxin ( PT ) , filamentous hemagglutinin , and pertactin . The results of the first period of follow-up , which ended in 1994 ( stage 1 ) , showed that both vaccines had a protective efficacy of 84 % in the first 2 years of life ; when the trial 's follow-up was extended under partial blinding until the participating children had reached 33 months of age ( stage 2 of the follow-up ) , these high levels of efficacy had persisted . Therefore , the objective of this study was to estimate the persistence of protection from 3 to 6 years of age of the 2 3-component DTaP vaccines administered as primary immunization in infancy . METHODS An unblinded prospect i ve longitudinal study of vaccinated and unvaccinated children in 4 Italian regions , with active surveillance of cough , was conducted by study nurses , and Bordetella pertussis infections were confirmed laboratory . The present study ( stage 3 ) included those children who completed stage 2 of the follow-up and were still under active surveillance as of October 1 , 1995 , accounting for 4217 children who had received DTaP SB ( representing 94 % of the vaccine 's recipients in the initial phase of the trial ) , 4215 who had received DTaP CB ( 95 % of the original recipients ) , and 266 who had received DT only ( 18 % of the original recipients ) . Because the parents of most of the original  DT placebo group accepted pertussis vaccination during stage 2 in 1995 , an additional 856 children were recruited in the DT group at the initiation of stage 3 . These additional children were identified from the census list of children born in the same period and living in the same areas as the trial participants but who had been vaccinated in infancy with DT only . Eligible children were included in stage 3 if they had no history of either pertussis or pertussis vaccination  and if a serum sample obtained at the time of enrollment had undetectable immunoglobulin G ( IgG ) against PT . Parental consent to participate in the study was obtained . Active surveillance for pertussis was conducted in the field by 72 study nurses through monthly contact with each family in the study . A cough episode that lasted > /=7 days was considered to be a laboratory-confirmed infection by Bordetella pertussis if at least 1 of the following 5 criteria ( listed in hierarchic order ) was met : 1 ) B pertussis was obtained from nasopharyngeal culture ( culture-confirmed infection ) ; 2 ) the enzyme-linked immunosorbent assay ( ELISA ) IgG or IgA titer against PT in the convalescent-phase serum sample increased by at least 100 % compared with the acute-phase sample ; 3 ) the PT-neutralizing titers in Chinese hamster ovary assay in the convalescent-phase sample increased by at least 4-fold compared with the acute-phase sample ; 4 ) the ELISA IgG or IgA titer against filamentous hemagglutinin in the convalescent-phase sample increased by at least 100 % and the culture or the polymerase chain reaction assay on the nasopharyngeal aspirate was negative for B parapertussis ; and 5 ) the ELISA IgG PT titer in 1 of the 2 serum sample s exceeded the geometric mean titer computed on convalescent sera of the children with a culture-confirmed B pertussis infection in each study group . Incidence of laboratory-confirmed B pertussis infection , using case definitions that varied in terms of duration and type of cough , was computed and the proportion of cases prevented among DTaP recipients in comparison with DT recipients was calculated . RESULTS A total of 391 laboratory-confirmed infections were identified in the 3-year follow-up period ( 138 DTaP SB , 126 DTaP CB , 127 DT recipients , respectively ) . The mean duration of cough in children  with laboratory-confirmed infection was 48 , 47 , and 70 days for the DTaP SB , DTaP CB , and DT recipients , respectively ; the mean duration of spasmodic cough was 15 , 13 , and 23 days , respectively . When using the primary case definition ( ie , laboratory-confirmed B pertussis infection and > /=14 days of spasmodic cough or > /=21 days of any cough ) , the efficacy was 78 % for the DTaP SB vaccine ( 95 % confidence interval [ CI ] : 71%-83 % ) and 81 % for the DTaP CB vaccine ( 95 % CI : 74%-85 % ) . When using the case definition based on a more severe clinical presentation ( > /=21 days of spasmodic cough ) , the vaccine efficacy was 86 % ( 95 % CI : 79%-91 % ) for both vaccines . When using the case definition based on milder clinical presentation ( any cough for > /=7 days ) , the efficacy was 76 % ( 95 % CI : 69%-81 % ) for the DTaP SB vaccine and 78 % ( 95 % CI : 72%-83 % ) for the DTaP CB vaccine . CONCLUSIONS The persistence of protection through 6 years of age suggests that the fourth DTaP dose could be postponed until preschool age in children who received 3-component acellular pertussis vaccines in infancy , provided that immunity to diphtheria and tetanus is maintained . Additional booster doses could be administered at older ages to reduce reactogenicity induced by multiple administrations and to optimize the control of pertussis in adolescents and young adults OBJECTIVE Monitor the long-term immunogenicity of a single dose of acellular pertussis vaccine in health-care workers . DESIGN German health-care workers and child-care workers received a single dose of a monovalent acellular pertussis vaccine ( PAC-Mérieux ) in an open-label study . Blood sample s were taken before ( n=261 ) , 4 weeks after ( n=246 ) , 1 year ( n=187 ) , 2 years ( n=53 ) , 3 years ( n=134 ) and 4 years ( n=37 ) after vaccination . IgG- and IgA-anti-pertussis-toxin ( PT ) , IgG- and IgA-anti-filamentous hemagglutinin ( FHA ) , and IgG-anti-pertactin ( PRN ) were measured by ELISA . RESULTS Of all subjects , 97.1 % , 99.2 % and 97.2 % had an antibody response to PT , FHA and PRN , respectively . Four weeks after vaccination the median titres of IgG antibodies to PT , FHA and PRN were 314 , 785 and 84 EU/l , respectively , and all vaccinees had an immune response to at least one pertussis antigen . IgA-anti-PT and IgA-anti-FHA responses were found in 63.4 % and 96.3 % of subjects with a median titre of 30 and 196 EU/ml , respectively . The titre of IgG-anti-PT decreased slowly with a median concentration of 76 , 71 , 71 and 63 EU/ml after 1 , 2 , 3 and 4 years , respectively . Secondary titre increases were observed in 0.5 % , 3.3 % , 5.6 % and 12.5 % of the vaccinees 1 , 2 , 3 , and 4 years after vaccination . CONCLUSION In German health paediatric care workers long-lasting immune responses with high antibody levels could be induced by a single dose of acellular pertussis vaccine . A renewed contact with B. pertussis antigens result ed in a measurable immune response to PT between 0.5 % ( 1 year p.v . ) and 12.5 % ( 4 years p.v . ) BACKGROUND Pertussis immunization of adults may be necessary to improve the control of a rising burden of disease and infection . This trial of an acellular pertussis vaccine among adolescents and adults evaluated the incidence of pertussis , vaccine safety , immunogenicity , and protective efficacy . METHODS Bordetella pertussis infections and illnesses were prospect ively assessed in 2781 healthy subjects between the ages of 15 and 65 years who were enrolled in a national multicenter , r and omized , double-blind trial of an acellular pertussis vaccine .  Subjects received either a dose of a tricomponent acellular pertussis vaccine or a hepatitis A vaccine ( control ) and were monitored for 2.5 years for illnesses with cough that lasted for more than 5 days . Each illness was evaluated with use of a nasopharyngeal aspirate for culture and polymerase-chain-reaction assay , and serum sample s from patients in both acute and convalescent stages of illness were analyzed for changes in antibodies to nine B. pertussis antigens . RESULTS Of the 2781 subjects , 1391 received the acellular pertussis vaccine  and 1390 received the control vaccine . The groups had similar ages and demographic characteristics , and the median duration of follow-up was 22 months . The acellular pertussis vaccine was safe and immunogenic . There were 2672 prolonged illnesses with cough , but the incidence of this nonspecific outcome did not vary between the groups , even when stratified according to age , season , and duration of cough . On the basis of the primary pertussis case definition , vaccine protection was 92 percent ( 95 percent confidence interval , 32 to 99 percent ) . Among unimmunized controls with illness , 0.7 percent to 5.7 percent had B. pertussis infection , and the percentage increased with the duration of cough . On the basis of other case definitions , the incidence of pertussis in the controls ranged from 370 to 450 cases per 100,000 person-years . CONCLUSIONS The acellular pertussis vaccine was protective among adolescents and adults , and its 
    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: A r and omized , double-blind trial comparing a diphtheria-tetanus-acellular pertussis vaccine ( DTaP ) ( pertussis toxoid and filamentous hemagglutinin ) with a whole-cell vaccine ( DTwP ) was conducted . A case-contact study was nested in the trial to estimate absolute efficacy . From 1990 through 1994 , 4181 children were r and omized to receive one of the vaccines at 2 , 4 , and 6 months .  Severe adverse events were monitored weekly during two visits after vaccination . Fewer serious adverse events were observed after DTaP. Surveillance for cough illnesses persisting more than 7 days , in children under 15 years of age , was made by weekly home visits . Examining physicians , blind to vaccination status , took sample s for culture and serologic testing . Pertussis was defined as 21 or more days of cough confirmed by culture , serology , or contact with a culture-confirmed person . Beginning 28 days after the third vaccine dose , the overall ratio of pertussis incidence in the DTaP group relative to the DTwP group ( RRac/wc ) was 1.54 ( 95 % CI , 1.23 - 1.93 ) . In children younger than 18 months of age , RRac/wc was 1.16 ( 95 % CI , 0.77 - 1.73 ) and 1.76 ( 95 % CI , 1.33 - 2.33 ) in children older than 18 months , which suggests a shorter duration of protection with the acellular vaccine ( P = 0.090 ) . Absolute efficacy estimates derived from the case-contact study confirmed the lower protection afforded by the acellular vaccine compared with the whole-cell vaccine : 31 % ( 95 % CI , 7 - 49 ) versus 55 % against the protocol case definition , and 85 % ( 95 % CI , 66 - 93 ) versus 96 % for the more severe WHO case definition . Although vaccination with DTaP provided a lower degree of protection than the highly effective DTwP , this difference was less prominent before 18 months of age , the customary age for a fourth dose . The safer DTaP vaccine may prove a valuable substitute for whole-cell vaccines when used in a schedule that includes a booster-dose BACKGROUND In 1992 - 1993 , a r and omized , double-blind , placebo-controlled clinical trial of two 3-component acellular pertussis vaccines was started in 4 of Italy 's 20 regions . During the trial , the children had been r and omized to receive 3 doses of 1 of 2 acellular pertussis vaccines combined with diphtheria and tetanus toxoids ( DT ) or of a DT vaccine only , at 2 , 4 , and 6 months of age . Both diphtheria-tetanus-acellular pertussis ( DTaP ) vaccines , 1 manufactured by SmithKline Beecham ( DTaP SB ; Infanrix ) and 1 manufactured by Chiron Biocine ( DTaP CB ; Triacelluvax ) , contain pertussis toxin ( PT ) , filamentous hemagglutinin , and pertactin . The results of the first period of follow-up , which ended in 1994 ( stage 1 ) , showed that both vaccines had a protective efficacy of 84 % in the first 2 years of life ; when the trial 's follow-up was extended under partial blinding until the participating children had reached 33 months of age ( stage 2 of the follow-up ) , these high levels of efficacy had persisted . Therefore , the objective of this study was to estimate the persistence of protection from 3 to 6 years of age of the 2 3-component DTaP vaccines administered as primary immunization in infancy . METHODS An unblinded prospect i ve longitudinal study of vaccinated and unvaccinated children in 4 Italian regions , with active surveillance of cough , was conducted by study nurses , and Bordetella pertussis infections were confirmed laboratory . The present study ( stage 3 ) included those children who completed stage 2 of the follow-up and were still under active surveillance as of October 1 , 1995 , accounting for 4217 children who had received DTaP SB ( representing 94 % of the vaccine 's recipients in the initial phase of the trial ) , 4215 who had received DTaP CB ( 95 % of the original recipients ) , and 266 who had received DT only ( 18 % of the original recipients ) . Because the parents of most of the original  DT placebo group accepted pertussis vaccination during stage 2 in 1995 , an additional 856 children were recruited in the DT group at the initiation of stage 3 . These additional children were identified from the census list of children born in the same period and living in the same areas as the trial participants but who had been vaccinated in infancy with DT only . Eligible children were included in stage 3 if they had no history of either pertussis or pertussis vaccination  and if a serum sample obtained at the time of enrollment had undetectable immunoglobulin G ( IgG ) against PT . Parental consent to participate in the study was obtained . Active surveillance for pertussis was conducted in the field by 72 study nurses through monthly contact with each family in the study . A cough episode that lasted > /=7 days was considered to be a laboratory-confirmed infection by Bordetella pertussis if at least 1 of the following 5 criteria ( listed in hierarchic order ) was met : 1 ) B pertussis was obtained from nasopharyngeal culture ( culture-confirmed infection ) ; 2 ) the enzyme-linked immunosorbent assay ( ELISA ) IgG or IgA titer against PT in the convalescent-phase serum sample increased by at least 100 % compared with the acute-phase sample ; 3 ) the PT-neutralizing titers in Chinese hamster ovary assay in the convalescent-phase sample increased by at least 4-fold compared with the acute-phase sample ; 4 ) the ELISA IgG or IgA titer against filamentous hemagglutinin in the convalescent-phase sample increased by at least 100 % and the culture or the polymerase chain reaction assay on the nasopharyngeal aspirate was negative for B parapertussis ; and 5 ) the ELISA IgG PT titer in 1 of the 2 serum sample s exceeded the geometric mean titer computed on convalescent sera of the children with a culture-confirmed B pertussis infection in each study group . Incidence of laboratory-confirmed B pertussis infection , using case definitions that varied in terms of duration and type of cough , was computed and the proportion of cases prevented among DTaP recipients in comparison with DT recipients was calculated . RESULTS A total of 391 laboratory-confirmed infections were identified in the 3-year follow-up period ( 138 DTaP SB , 126 DTaP CB , 127 DT recipients , respectively ) . The mean duration of cough in children  with laboratory-confirmed infection was 48 , 47 , and 70 days for the DTaP SB , DTaP CB , and DT recipients , respectively ; the mean duration of spasmodic cough was 15 , 13 , and 23 days , respectively . When using the primary case definition ( ie , laboratory-confirmed B pertussis infection and > /=14 days of spasmodic cough or > /=21 days of any cough ) , the efficacy was 78 % for the DTaP SB vaccine ( 95 % confidence interval [ CI ] : 71%-83 % ) and 81 % for the DTaP CB vaccine ( 95 % CI : 74%-85 % ) . When using the case definition based on a more severe clinical presentation ( > /=21 days of spasmodic cough ) , the vaccine efficacy was 86 % ( 95 % CI : 79%-91 % ) for both vaccines . When using the case definition based on milder clinical presentation ( any cough for > /=7 days ) , the efficacy was 76 % ( 95 % CI : 69%-81 % ) for the DTaP SB vaccine and 78 % ( 95 % CI : 72%-83 % ) for the DTaP CB vaccine . CONCLUSIONS The persistence of protection through 6 years of age suggests that the fourth DTaP dose could be postponed until preschool age in children who received 3-component acellular pertussis vaccines in infancy , provided that immunity to diphtheria and tetanus is maintained . Additional booster doses could be administered at older ages to reduce reactogenicity induced by multiple administrations and to optimize the control of pertussis in adolescents and young adults OBJECTIVE Monitor the long-term immunogenicity of a single dose of acellular pertussis vaccine in health-care workers . DESIGN German health-care workers and child-care workers received a single dose of a monovalent acellular pertussis vaccine ( PAC-Mérieux ) in an open-label study . Blood sample s were taken before ( n=261 ) , 4 weeks after ( n=246 ) , 1 year ( n=187 ) , 2 years ( n=53 ) , 3 years ( n=134 ) and 4 years ( n=37 ) after vaccination . IgG- and IgA-anti-pertussis-toxin ( PT ) , IgG- and IgA-anti-filamentous hemagglutinin ( FHA ) , and IgG-anti-pertactin ( PRN ) were measured by ELISA . RESULTS Of all subjects , 97.1 % , 99.2 % and 97.2 % had an antibody response to PT , FHA and PRN , respectively . Four weeks after vaccination the median titres of IgG antibodies to PT , FHA and PRN were 314 , 785 and 84 EU/l , respectively , and all vaccinees had an immune response to at least one pertussis antigen . IgA-anti-PT and IgA-anti-FHA responses were found in 63.4 % and 96.3 % of subjects with a median titre of 30 and 196 EU/ml , respectively . The titre of IgG-anti-PT decreased slowly with a median concentration of 76 , 71 , 71 and 63 EU/ml after 1 , 2 , 3 and 4 years , respectively . Secondary titre increases were observed in 0.5 % , 3.3 % , 5.6 % and 12.5 % of the vaccinees 1 , 2 , 3 , and 4 years after vaccination . CONCLUSION In German health paediatric care workers long-lasting immune responses with high antibody levels could be induced by a single dose of acellular pertussis vaccine . A renewed contact with B. pertussis antigens result ed in a measurable immune response to PT between 0.5 % ( 1 year p.v . ) and 12.5 % ( 4 years p.v . ) BACKGROUND Pertussis immunization of adults may be necessary to improve the control of a rising burden of disease and infection . This trial of an acellular pertussis vaccine among adolescents and adults evaluated the incidence of pertussis , vaccine safety , immunogenicity , and protective efficacy . METHODS Bordetella pertussis infections and illnesses were prospect ively assessed in 2781 healthy subjects between the ages of 15 and 65 years who were enrolled in a national multicenter , r and omized , double-blind trial of an acellular pertussis vaccine .  Subjects received either a dose of a tricomponent acellular pertussis vaccine or a hepatitis A vaccine ( control ) and were monitored for 2.5 years for illnesses with cough that lasted for more than 5 days . Each illness was evaluated with use of a nasopharyngeal aspirate for culture and polymerase-chain-reaction assay , and serum sample s from patients in both acute and convalescent stages of illness were analyzed for changes in antibodies to nine B. pertussis antigens . RESULTS Of the 2781 subjects , 1391 received the acellular pertussis vaccine  and 1390 received the control vaccine . The groups had similar ages and demographic characteristics , and the median duration of follow-up was 22 months . The acellular pertussis vaccine was safe and immunogenic . There were 2672 prolonged illnesses with cough , but the incidence of this nonspecific outcome did not vary between the groups , even when stratified according to age , season , and duration of cough . On the basis of the primary pertussis case definition , vaccine protection was 92 percent ( 95 percent confidence interval , 32 to 99 percent ) . Among unimmunized controls with illness , 0.7 percent to 5.7 percent had B. pertussis infection , and the percentage increased with the duration of cough . On the basis of other case definitions , the incidence of pertussis in the controls ranged from 370 to 450 cases per 100,000 person-years . CONCLUSIONS The acellular pertussis vaccine was protective among adolescents and adults , and its 
    Output:
    