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: BACKGROUND In the US , it is recommended that 4 - 6 year old children receive diphtheria-tetanus-acellular pertussis ( DTaP ) , inactivated poliovirus ( IPV ) , measles-mumps-rubella ( MMR ) , varicella ( V ) , and influenza vaccines . Data relating to the concomitant administration of combination DTaP-IPV vaccine ( Kinrix ™ ; GlaxoSmithKline Biologicals ) and influenza or V vaccines are currently limited . This study was undertaken to evaluate the immunogenicity and reactogenicity of Kinrix ™ when co-administered with MMR ( M-M-RII ( ® ) , Merck & Co. ) and Varivax ™ ( Merck & Co. ) in 4 - 6 year old children . METHODS Phase IIIb , open-label , non-inferiority study ( NCT00871117 ) . We r and omized ( 1:1 ) healthy 4 - 6 year olds to receive Kinrix ™ +MMR+V on day 0 ( Group 1 ) , or Kinrix ™ +MMR on day 0 , followed by V at month 1 ( Group 2 ) . We measured  DTaP-IPV immunogenicity before and 1 month post-vaccination ( prior to V vaccination in Group 2 ) . We collected local and general solicited symptoms within 4 days after vaccination and serious adverse events ( SAEs ) through 6 months post-vaccination . RESULTS We enrolled 478 subjects . One month post-vaccination , > 95 % of subjects in both groups had booster responses to diphtheria , tetanus and pertussis antigens and all subjects had seroprotective anti-poliovirus antibody titers . Immune responses in Group 1 were non-inferior to Group 2 for responses to DTaP-IPV antigens according to pre-specified criteria . Reporting of solicited local events at the DTaP-IPV site appeared to be similar between the two vaccine groups , as was reporting of solicited general adverse events within 4 days of vaccination ; no vaccine related SAEs were reported . CONCLUSION Concomitant administration of varicella vaccine with Kinrix ™ and MMR  did not impact the immunogenicity of diphtheria , tetanus , pertussis or poliovirus antigens . Both vaccine regimens were well tolerated . These results support the co-administration of DTaP-IPV , MMR , and V vaccines in 4 - 6-year-old children , providing protection against multiple diseases in a timely and efficient manner BACKGROUND The introduction of the inactivated poliovirus vaccine ( IPV ) represents a crucial step in the polio eradication endgame . This trial examined the safety and immunogenicity of IPV given alongside the measles-rubella and yellow fever vaccines at 9 months and when given as a full or fractional dose using needle and syringe or disposable-syringe jet injector . METHODS We did a phase 4 , r and omised , non-inferiority trial at three periurban government clinics in west Gambia . Infants aged 9 - 10 months who had already received oral poliovirus vaccine were r and omly assigned to receive the IPV , measles-rubella , and yellow fever vaccines , singularly or in combination . Separately , IPV was given as a full intramuscular or fractional intradermal dose by needle and syringe or disposable-syringe jet injector at a second visit . The primary outcomes were seroprevalence rates for poliovirus 4 - 6 weeks post-vaccination and the rate of seroconversion between baseline and post-vaccination serum sample s for measles , rubella , and yellow fever ; and the post-vaccination antibody titres generated against each component of the vaccines . We did a per- protocol analysis with a non-inferiority margin of 10 % for poliovirus seroprevalence and measles , rubella , and yellow fever seroconversion , and ( 1/3 ) log2 for log2-transformed antibody titres . This trial is registered with Clinical Trials.gov , number NCT01847872 . FINDINGS Between July 10 , 2013 , and May 8 , 2014 , we assessed 1662 infants for eligibility , of whom 1504 were enrolled into one of seven groups for vaccine interference and one of four groups for fractional dosing and alternative route of administration . The rubella and yellow fever antibody titres were reduced by co-administration but the seroconversion rates achieved non-inferiority in both cases ( rubella , -4·5 % [ 95 % CI -9·5 to -0·1 ] ; yellow fever , 1·2 % [ -2·9 to 5·5 ] ) . Measles and poliovirus responses were unaffected ( measles , 6·8 % [ 95 % CI -1·4 to 14·9 ] ; poliovirus serotype 1 , 1·6 % [ -6·7 to 4·7 ] ; serotype 2 , 0·0 % [ -2·1 to 2·1 ] ; serotype 3 , 0·0 % [ -3·8 to 3·9 ] ) . Poliovirus seroprevalence was universally high ( > 97 % ) after vaccination , but the antibody titres generated by fractional intradermal doses of IPV did not achieve non-inferiority compared with full dose . The number of infants who seroconverted or had a four-fold rise in titres was also lower by the intradermal route . There were no safety concerns . INTERPRETATION The data support the future co-administration of IPV , measles-rubella , and yellow fever vaccines within the Exp and ed Programme on Immunization schedule at 9 months . The administration of single fractional intradermal doses of IPV by needle and syringe or disposable-syringe jet injector compromises the immunity generated , although it results in a high post-vaccination poliovirus seroprevalence . FUNDING Bill & Melinda Gates Foundation Background Fractional-dose administration of inactivated poliovirus vaccine ( fIPV ) could increase IPV affordability and stretch limited supplies . We assessed immune responses following fIPV administered intradermally , compared with full-dose IPV administered intramuscularly , among adults with a history of oral poliovirus vaccine ( OPV ) receipt . Methods We conducted a r and omized , controlled noninferiority trial in Cuba .  fIPV or IPV were administered on days 0 and 28 ; serum was collected on days 0 , 7 , 28 , and 56 for analysis by a neutralization assay . The primary end point was seroconversion or a ≥4-fold rise in antibody titer . The noninferiority limit was 10 % . The secondary end point was safety , assessed by the number and intensity of adverse reactions . Results A total of 503 of 534 enrolled participants ( 94.2 % ) completed all study requirements . Twenty-eight days after the first dose , 94.8 % , 98.0 % , and 98.0 % of fIPV recipients had an immune response to poliovirus types 1 , 2 , and 3 , respectively , compared with 98.1 % ( P = .06 ) , 98.0 % ( P = 1.00 ) , and 99.2 % ( P = .45 ) in the IPV arm . Noninferiority was achieved on days 7 , 28 , and 56 for all serotypes . No serious adverse events were reported . Conclusion fIPV induced similar boosting immune responses , compared with full-dose IPV . This suggests that fIPV would be an effective strategy to boost population immunity in an outbreak situation . Clinical Trials Registration ACTRN12615000305527 BACKGROUND Bivalent oral poliovirus vaccine ( bOPV ; types 1 and 3 ) is expected to replace trivalent OPV ( tOPV ) globally by April , 2016 , preceded by the introduction of at least one dose of inactivated poliovirus vaccine ( IPV ) in routine immunisation programmes to eliminate vaccine-associated or vaccine-derived poliomyelitis from serotype 2 poliovirus . Because data are needed on sequential IPV-bOPV schedules , we assessed the immunogenicity of two different IPV-bOPV schedules compared with an all-IPV schedule in infants . METHODS We did a r and omised , controlled , open-label , non-inferiority trial with healthy , full-term ( > 2·5 kg birthweight ) infants aged 8 weeks ( ± 7 days ) at six well-child clinics in Santiago , Chile . We used supplied lists to r and omly assign infants ( 1:1:1 ) to receive three polio vaccinations ( IPV by injection or bOPV as oral drops ) at age 8 , 16 , and 24 weeks in one of three sequential schedules : IPV-bOPV-bOPV , IPV-IPV-bOPV , or IPV-IPV-IPV . We did the r and omisation with blocks of 12 stratified by study site . All analyses were done in a masked manner . Co- primary outcomes were non-inferiority of the bOPV-containing schedules compared with the all-IPV schedule for seroconversion ( within a 10 % margin ) and antibody titres ( within two-thirds log2 titres ) to poliovirus serotypes 1 and 3 at age 28 weeks , analysed in the per- protocol population . Secondary outcomes were seroconversion and titres to serotype 2 and faecal shedding for 4 weeks after a monovalent OPV type 2 challenge at age 28 weeks . Safety analyses were done in the intention-to-treat population . This trial is registered with Clinical Trials.gov , number NCT01841671 , and is closed to new participants . FINDINGS Between April 25 and August 1 , 2013 , we assigned 570 infants to treatment : 190 to IPV-bOPV-bOPV  , 192 to IPV-IPV-bOPV  , and 188  to IPV-IPV-IPV . 564 ( 99 % ) were vaccinated and included in the intention-to-treat cohort , and 537 ( 94 % ) in the per- protocol analyses . In the IPV-bOPV-bOPV , IPV-IPV-bOPV , and IPV-IPV-IPV groups , respectively , the proportions of children with seroconversion to type 1 poliovirus were 166 ( 98·8 % ) of 168 , 95 % CI 95·8 - 99·7 ; 178 ( 100 % ) , 97·9 - 100·0 ; and 175 ( 100 % ) , 97·9 - 100·0 . Proportions with seroconvsion to type 3 poliovirus were 163 ( 98·2 % ) of 166 , 94·8 - 99·4 ; 177 ( 100 % ) , 97·9 - 100·0 , and 172 ( 98·9 % ) of 174 , 95·9 - 99·7 . Non-inferiority was thus shown for the bOPV-containing schedules compared with the all-IPV schedule , with no significant differences between groups . In the IPV-bOPV-bOPV , IPV-IPV-bOPV , and IPV-IPV-IPV  groups , respectively , the proportions of children with seroprotective antibody titres to type 1 poliovirus were 168 ( 98·8 % ) of 170 , 95 % CI 95·8 - 99·7 ; 181 ( 100 % ) , 97·9 - 100·0 ; and 177 ( 100 % ) , 97·9 - 100·0 . Proportions to type 3 poliovirus were 166 ( 98·2 % ) of 169 , 94·9 - 99·4 ; 180 ( 100 % ) , 97·9 - 100·0 ; and 174 ( 98·9 % ) of 176 , 96·0 - 99·7 . Non-inferiority comparisons could not be done for this outcome because median titres for the groups receiving OPV were greater than the assay 's upper limit of detection ( log2 titres > 10·5 ) . The proportions of children seroconverting to type 2 poliovirus in the IPV-bOPV-bOPV , IPV-IPV-bOPV , and IPV-IPV-IPV groups , respectively , were 130 ( 77·4 % ) of 168 , 95 % CI 70·5 - 83·0 ; 169 ( 96·0 % ) of 176 , 92·0 - 98·0 ; and 175 ( 100 % ) , 97·8  - 100 . IPV-bOPV schedules result ed in almost a 0·3 log reduction of type 2 faecal shedding compared with the IPV-only schedule . No participants died during the trial ; 81 serious adverse events were reported , of which one was thought to be possibly vaccine-related 
    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: BACKGROUND In the US , it is recommended that 4 - 6 year old children receive diphtheria-tetanus-acellular pertussis ( DTaP ) , inactivated poliovirus ( IPV ) , measles-mumps-rubella ( MMR ) , varicella ( V ) , and influenza vaccines . Data relating to the concomitant administration of combination DTaP-IPV vaccine ( Kinrix ™ ; GlaxoSmithKline Biologicals ) and influenza or V vaccines are currently limited . This study was undertaken to evaluate the immunogenicity and reactogenicity of Kinrix ™ when co-administered with MMR ( M-M-RII ( ® ) , Merck & Co. ) and Varivax ™ ( Merck & Co. ) in 4 - 6 year old children . METHODS Phase IIIb , open-label , non-inferiority study ( NCT00871117 ) . We r and omized ( 1:1 ) healthy 4 - 6 year olds to receive Kinrix ™ +MMR+V on day 0 ( Group 1 ) , or Kinrix ™ +MMR on day 0 , followed by V at month 1 ( Group 2 ) . We measured  DTaP-IPV immunogenicity before and 1 month post-vaccination ( prior to V vaccination in Group 2 ) . We collected local and general solicited symptoms within 4 days after vaccination and serious adverse events ( SAEs ) through 6 months post-vaccination . RESULTS We enrolled 478 subjects . One month post-vaccination , > 95 % of subjects in both groups had booster responses to diphtheria , tetanus and pertussis antigens and all subjects had seroprotective anti-poliovirus antibody titers . Immune responses in Group 1 were non-inferior to Group 2 for responses to DTaP-IPV antigens according to pre-specified criteria . Reporting of solicited local events at the DTaP-IPV site appeared to be similar between the two vaccine groups , as was reporting of solicited general adverse events within 4 days of vaccination ; no vaccine related SAEs were reported . CONCLUSION Concomitant administration of varicella vaccine with Kinrix ™ and MMR  did not impact the immunogenicity of diphtheria , tetanus , pertussis or poliovirus antigens . Both vaccine regimens were well tolerated . These results support the co-administration of DTaP-IPV , MMR , and V vaccines in 4 - 6-year-old children , providing protection against multiple diseases in a timely and efficient manner BACKGROUND The introduction of the inactivated poliovirus vaccine ( IPV ) represents a crucial step in the polio eradication endgame . This trial examined the safety and immunogenicity of IPV given alongside the measles-rubella and yellow fever vaccines at 9 months and when given as a full or fractional dose using needle and syringe or disposable-syringe jet injector . METHODS We did a phase 4 , r and omised , non-inferiority trial at three periurban government clinics in west Gambia . Infants aged 9 - 10 months who had already received oral poliovirus vaccine were r and omly assigned to receive the IPV , measles-rubella , and yellow fever vaccines , singularly or in combination . Separately , IPV was given as a full intramuscular or fractional intradermal dose by needle and syringe or disposable-syringe jet injector at a second visit . The primary outcomes were seroprevalence rates for poliovirus 4 - 6 weeks post-vaccination and the rate of seroconversion between baseline and post-vaccination serum sample s for measles , rubella , and yellow fever ; and the post-vaccination antibody titres generated against each component of the vaccines . We did a per- protocol analysis with a non-inferiority margin of 10 % for poliovirus seroprevalence and measles , rubella , and yellow fever seroconversion , and ( 1/3 ) log2 for log2-transformed antibody titres . This trial is registered with Clinical Trials.gov , number NCT01847872 . FINDINGS Between July 10 , 2013 , and May 8 , 2014 , we assessed 1662 infants for eligibility , of whom 1504 were enrolled into one of seven groups for vaccine interference and one of four groups for fractional dosing and alternative route of administration . The rubella and yellow fever antibody titres were reduced by co-administration but the seroconversion rates achieved non-inferiority in both cases ( rubella , -4·5 % [ 95 % CI -9·5 to -0·1 ] ; yellow fever , 1·2 % [ -2·9 to 5·5 ] ) . Measles and poliovirus responses were unaffected ( measles , 6·8 % [ 95 % CI -1·4 to 14·9 ] ; poliovirus serotype 1 , 1·6 % [ -6·7 to 4·7 ] ; serotype 2 , 0·0 % [ -2·1 to 2·1 ] ; serotype 3 , 0·0 % [ -3·8 to 3·9 ] ) . Poliovirus seroprevalence was universally high ( > 97 % ) after vaccination , but the antibody titres generated by fractional intradermal doses of IPV did not achieve non-inferiority compared with full dose . The number of infants who seroconverted or had a four-fold rise in titres was also lower by the intradermal route . There were no safety concerns . INTERPRETATION The data support the future co-administration of IPV , measles-rubella , and yellow fever vaccines within the Exp and ed Programme on Immunization schedule at 9 months . The administration of single fractional intradermal doses of IPV by needle and syringe or disposable-syringe jet injector compromises the immunity generated , although it results in a high post-vaccination poliovirus seroprevalence . FUNDING Bill & Melinda Gates Foundation Background Fractional-dose administration of inactivated poliovirus vaccine ( fIPV ) could increase IPV affordability and stretch limited supplies . We assessed immune responses following fIPV administered intradermally , compared with full-dose IPV administered intramuscularly , among adults with a history of oral poliovirus vaccine ( OPV ) receipt . Methods We conducted a r and omized , controlled noninferiority trial in Cuba .  fIPV or IPV were administered on days 0 and 28 ; serum was collected on days 0 , 7 , 28 , and 56 for analysis by a neutralization assay . The primary end point was seroconversion or a ≥4-fold rise in antibody titer . The noninferiority limit was 10 % . The secondary end point was safety , assessed by the number and intensity of adverse reactions . Results A total of 503 of 534 enrolled participants ( 94.2 % ) completed all study requirements . Twenty-eight days after the first dose , 94.8 % , 98.0 % , and 98.0 % of fIPV recipients had an immune response to poliovirus types 1 , 2 , and 3 , respectively , compared with 98.1 % ( P = .06 ) , 98.0 % ( P = 1.00 ) , and 99.2 % ( P = .45 ) in the IPV arm . Noninferiority was achieved on days 7 , 28 , and 56 for all serotypes . No serious adverse events were reported . Conclusion fIPV induced similar boosting immune responses , compared with full-dose IPV . This suggests that fIPV would be an effective strategy to boost population immunity in an outbreak situation . Clinical Trials Registration ACTRN12615000305527 BACKGROUND Bivalent oral poliovirus vaccine ( bOPV ; types 1 and 3 ) is expected to replace trivalent OPV ( tOPV ) globally by April , 2016 , preceded by the introduction of at least one dose of inactivated poliovirus vaccine ( IPV ) in routine immunisation programmes to eliminate vaccine-associated or vaccine-derived poliomyelitis from serotype 2 poliovirus . Because data are needed on sequential IPV-bOPV schedules , we assessed the immunogenicity of two different IPV-bOPV schedules compared with an all-IPV schedule in infants . METHODS We did a r and omised , controlled , open-label , non-inferiority trial with healthy , full-term ( > 2·5 kg birthweight ) infants aged 8 weeks ( ± 7 days ) at six well-child clinics in Santiago , Chile . We used supplied lists to r and omly assign infants ( 1:1:1 ) to receive three polio vaccinations ( IPV by injection or bOPV as oral drops ) at age 8 , 16 , and 24 weeks in one of three sequential schedules : IPV-bOPV-bOPV , IPV-IPV-bOPV , or IPV-IPV-IPV . We did the r and omisation with blocks of 12 stratified by study site . All analyses were done in a masked manner . Co- primary outcomes were non-inferiority of the bOPV-containing schedules compared with the all-IPV schedule for seroconversion ( within a 10 % margin ) and antibody titres ( within two-thirds log2 titres ) to poliovirus serotypes 1 and 3 at age 28 weeks , analysed in the per- protocol population . Secondary outcomes were seroconversion and titres to serotype 2 and faecal shedding for 4 weeks after a monovalent OPV type 2 challenge at age 28 weeks . Safety analyses were done in the intention-to-treat population . This trial is registered with Clinical Trials.gov , number NCT01841671 , and is closed to new participants . FINDINGS Between April 25 and August 1 , 2013 , we assigned 570 infants to treatment : 190 to IPV-bOPV-bOPV  , 192 to IPV-IPV-bOPV  , and 188  to IPV-IPV-IPV . 564 ( 99 % ) were vaccinated and included in the intention-to-treat cohort , and 537 ( 94 % ) in the per- protocol analyses . In the IPV-bOPV-bOPV , IPV-IPV-bOPV , and IPV-IPV-IPV groups , respectively , the proportions of children with seroconversion to type 1 poliovirus were 166 ( 98·8 % ) of 168 , 95 % CI 95·8 - 99·7 ; 178 ( 100 % ) , 97·9 - 100·0 ; and 175 ( 100 % ) , 97·9 - 100·0 . Proportions with seroconvsion to type 3 poliovirus were 163 ( 98·2 % ) of 166 , 94·8 - 99·4 ; 177 ( 100 % ) , 97·9 - 100·0 , and 172 ( 98·9 % ) of 174 , 95·9 - 99·7 . Non-inferiority was thus shown for the bOPV-containing schedules compared with the all-IPV schedule , with no significant differences between groups . In the IPV-bOPV-bOPV , IPV-IPV-bOPV , and IPV-IPV-IPV  groups , respectively , the proportions of children with seroprotective antibody titres to type 1 poliovirus were 168 ( 98·8 % ) of 170 , 95 % CI 95·8 - 99·7 ; 181 ( 100 % ) , 97·9 - 100·0 ; and 177 ( 100 % ) , 97·9 - 100·0 . Proportions to type 3 poliovirus were 166 ( 98·2 % ) of 169 , 94·9 - 99·4 ; 180 ( 100 % ) , 97·9 - 100·0 ; and 174 ( 98·9 % ) of 176 , 96·0 - 99·7 . Non-inferiority comparisons could not be done for this outcome because median titres for the groups receiving OPV were greater than the assay 's upper limit of detection ( log2 titres > 10·5 ) . The proportions of children seroconverting to type 2 poliovirus in the IPV-bOPV-bOPV , IPV-IPV-bOPV , and IPV-IPV-IPV groups , respectively , were 130 ( 77·4 % ) of 168 , 95 % CI 70·5 - 83·0 ; 169 ( 96·0 % ) of 176 , 92·0 - 98·0 ; and 175 ( 100 % ) , 97·8  - 100 . IPV-bOPV schedules result ed in almost a 0·3 log reduction of type 2 faecal shedding compared with the IPV-only schedule . No participants died during the trial ; 81 serious adverse events were reported , of which one was thought to be possibly vaccine-related 
    Output:
    