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 Immunologic development of soy-fed infants has not been extensively studied . Early studies of soy flour – based formulas showed decreased immunoglobulin production when soy protein intake was limited . However , there were no significant differences in rotavirus vaccine responses between breast-fed and soy protein isolate – based formula-fed infants .  Nucleotides added to milk-based formula benefit infant immune status , but reports of the immunologic effects of adding nucleotides to soy-based formula are not available . This study evaluated immune status and morbidity of infants fed soy protein isolate formulas with and without added nucleotides for 1 year . Methods Newborn , term infants enrolled in a masked 12-month feeding trial were assigned r and omly to groups fed soy formula with or without added nucleotides ( n = 94 , n = 92 ) . A nonr and omized human milk/formula cohort ( n = 81 ) was concurrently enrolled . Recommended immunizations were administered at 2 , 4 , and 6 months . Immune status was determined from antibody responses to Haemophilus influenzae type b , tetanus , diphtheria , and poliovirus vaccines at 6 , 7 , and 12 months . Parents and physicians reported morbidity data . Results All vaccine responses were within normal ranges . No response differences were observed between infants fed soy formula and those fed nucleotide-supplemented soy . However , antibody to H. influenzae type b at 7 and 12 months was higher in infants fed nucleotide-supplemented soy than in infants fed human milk/formula ( P = 0.007 , P = 0.008 , respectively ) . Human milk/formula-fed infants had higher poliovirus neutralizing antibody at 12 months than did soy-fed infants ( P = 0.016 ) . Morbidity analyses showed that only physician-reported diarrhea was different among groups ( groups fed human milk/formula had less diarrhea than did soy groups , P = 0.011 ) . Conclusions Term infants fed soy protein isolate – based formulas  have normal immune development as measured by antibody responses to childhood immunizations Background . Rotavirus ( RV ) is the leading cause of diarrhea-related death in children worldwide and 95 % of RV-associated deaths occur in Africa and Asia where RV vaccines ( RVVs ) have lower efficacy . We hypothesize that differences in intestinal microbiome composition correlate with the decreased RVV efficacy observed in poor setting s. Methods . We conducted a nested , case-control study comparing prevaccination , fecal microbiome compositions between 6-week old , matched RVV responders and nonresponders in rural Ghana . These infants ' microbiomes were then compared with 154 age-matched , healthy Dutch infants ' microbiomes , assumed to be RVV responders .  Fecal microbiome analysis was performed in all groups using the Human Intestinal Tract Chip . Results . We analyzed findings in 78 Ghanaian infants , including 39 RVV responder and nonresponder pairs . The overall microbiome composition was significantly different between RVV responders and nonresponders ( FDR , 0.12 ) , and Ghanaian responders were more similar to Dutch infants than nonresponders ( P = .002 ) . RVV response correlated with an increased abundance of Streptococcus bovis and a decreased abundance of the Bacteroidetes phylum in comparisons between both Ghanaian RVV responders and nonresponders ( FDR , 0.008 vs 0.003 ) and Dutch infants and Ghanaian nonresponders ( FDR , 0.002 vs 0.009 ) . Conclusions . The intestinal microbiome composition correlates significantly with RVV immunogenicity and may contribute to the diminished RVV immunogenicity observed in developing countries A vaccination trial , performed on 86 3-month-old infants , has shown that the ability of the RIT 4237 live attenuated rotavirus strain to induce seroconversion is dramatically reduced when administered with live poliovirus vaccine . In a subsequent trial performed on 93 infants the attempt to overcome the poliovirus interference by administering two doses of associated vaccines was unsuccessful . No interference by the RIT 4237 strain on live attenuated polioviruses was observed Background A strategy of administering a neonatal rotavirus vaccine at birth to target early prevention of rotavirus gastroenteritis may address some of the barriers to global implementation of a rotavirus vaccine . Methods We conducted a r and omized , double‐blind , placebo‐controlled trial in Indonesia to evaluate the efficacy of an oral human neonatal rotavirus vaccine ( RV3‐BB ) in preventing rotavirus gastroenteritis . Healthy newborns received three doses of RV3‐BB , administered according to a neonatal schedule ( 0 to 5 days , 8 weeks , and 14 weeks of age ) or an infant schedule ( 8 weeks , 14 weeks , and 18 weeks of age ) , or placebo . The primary analysis was conducted in the per‐ protocol population , which included only participants who received all four doses of vaccine or placebo within the visit windows , with secondary analyses performed in the intention‐to‐treat population , which included all participants who underwent r and omization . Results Among the 1513 participants in the per‐ protocol population , severe rotavirus gastroenteritis occurred up to the age of 18 months in 5.6 % of the participants in the placebo group ( 28 of 504 babies ) , in 1.4 % in the neonatal‐schedule vaccine group ( 7 of 498 ) , and in 2.7 % in the infant‐schedule vaccine group ( 14 of 511 ) . This result ed in a vaccine efficacy of 75 % ( 95 % confidence interval [ CI ] , 44 to 91 ) in the neonatal‐schedule group ( P<0.001 ) , 51 % ( 95 % CI , 7 to 76 ) in the infant‐schedule group ( P=0.03 ) , and 63 % ( 95 % CI , 34 to 80 ) in the neonatal‐schedule and infant‐schedule groups combined ( combined vaccine group ) ( P<0.001 ) . Similar results were observed in the intention‐to‐treat analysis ( 1649 participants ) ; the vaccine efficacy was 68 % ( 95 % CI , 35 to 86 ) in the neonatal‐schedule group ( P=0.001 ) , 52 % ( 95 % CI , 11 to 76 ) in the infant‐schedule group ( P=0.02 ) , and 60 % ( 95 % CI , 31 to 76 ) in the combined vaccine group ( P<0.001 ) . Vaccine response , as evidence d by serum immune response or shedding of RV3‐BB in the stool , occurred in 78 of 83 participants ( 94 % ) in the neonatal‐schedule group and in 83 of 84 participants ( 99 % ) in the infant‐schedule group . The incidence of adverse events was similar across the groups . No episodes of intussusception occurred within the 21‐day risk period after administration of any dose of vaccine or placebo , and one episode of intussusception occurred 114 days after the third dose of vaccine in the infant‐schedule group . Conclusions RV3‐BB was efficacious in preventing severe rotavirus gastroenteritis when administered according to a neonatal or an infant schedule in Indonesia . ( Funded by the Bill and Melinda Gates Foundation and others ; Australian New Zeal and Clinical Trials Registry number , ACTRN12612001282875 . BACKGROUND Oral poliovirus vaccine is less immunogenic and effective in low-income countries than in high-income countries , similarly to other oral vaccines . The high prevalence of intestinal pathogens and associated environmental enteropathy has been proposed to explain this problem . Because administration of an antibiotic has the potential to resolve environmental enteropathy and clear bacterial pathogens , we aim ed to assess whether antibiotics would improve oral poliovirus vaccine immunogenicity . METHODS We did a double-blind , r and omised , placebo-controlled trial of the effect of azithromycin on the immunogenicity of serotype-3 monovalent oral poliovirus vaccine given to healthy infants living in 14 blocks of Vellore district , India . Infants were eligible to participate if they were 6 - 11 months old , available for the study duration , and lacked serum neutralising antibodies to serotype-3 poliovirus . Infants were r and omly assigned ( 1:1 ) at enrolment to receive oral 10 mg/kg azithromycin or placebo once daily for 3 days , followed by serotype-3 monovalent oral poliovirus vaccine on day 14 . The primary outcome was detection of serum neutralising antibodies to serotype-3 poliovirus at a dilution of one in eight or more on day 35 and was assessed in the per- protocol population ( ie , all those who received azithromycin or placebo , oral poliovirus vaccine , and provided a blood sample according to the study protocol ) . Safety outcomes were assessed in all infants enrolled in the study . The trial is registered with the Clinical Trials Registry India , number CTRI/2014/05/004588 . FINDINGS Between Aug 5 , 2014 , and March 21 , 2015 , 754 infants were r and omly assigned : 376 to receive azithromycin and 378 to placebo . Of these , 348 ( 93 % ) of 376 in the azithromycin group and 357 ( 94 % ) of 378 infants in the placebo group completed the study per protocol . In the azithromycin group , 175 ( 50 % ) seroconverted to serotype-3 poliovirus compared with 192 ( 54 % ) in the placebo group ( risk ratio 0·94 , 95 % CI 0·81 - 1·08 ; p=0·366 ) . Azithromycin  reduced faecal biomarkers of environmental enteropathy ( calprotectin , myeloperoxidase , α1-antitrypsin ) and the prevalence of bacterial but not viral or eukaryotic pathogens . Viral pathogens were associated with lower seroconversion . Three serious adverse events were reported ( two in the azithromycin group and one in the placebo group ) , but none was considered related to the study interventions . INTERPRETATION Azithromycin did not improve the immunogenicity of oral poliovirus vaccine despite reducing biomarkers of environmental enteropathy and the prevalence of pathogenic intestinal bacteria . Viral interference and innate antiviral immune mechanisms might be more important determinants of the immunogenicity of live-virus oral vaccines . FUNDING Bill & Melinda Gates Foundation Abstract Background Rotavirus (RV)–specific immunoglobulin A ( IgA ) responses following oral RV vaccination are impaired in low-income countries , where the utility of RV-IgA as a correlate of protection ( CoP ) remains unclear . In a monovalent oral RV vaccine ( Rotarix ) efficacy trial among infants in Dhaka , Bangladesh , we identified factors associated with poor RV-IgA responses and explored the utility of RV-IgA as a CoP. Methods Infants were r and omized to receive Rotarix or no Rotarix at 10 and 17 weeks of life and followed with active diarrheal surveillance .  RV-IgA concentration , seroconversion , and seropositivity were determined at 18 weeks of life and analyzed for correlation(s ) with rotavirus diarrhea ( RVD ) and for contribution to Rotarix vaccine effect . Results Among vaccinated infants , overall RV-IgA geometric mean concentration was 21 U/mL ; only 27 % seroconverted and 32 % were seropositive after vaccination . Increased RV-specific maternal antibodies significantly impaired immunogenicity . Seroconversion was associated with reduced risk of RVD through 1 year of life , but RV-IgA seropositivity only explained 7.8 % of the vaccine effect demonstrated by the clinical endpoint ( RVD ) . Conclusions RV-IgA responses were low among infants in Bangladesh and were significantly impaired by maternal antibodies . RV-IgA is a suboptimal CoP in this setting ; an improved CoP for RV in low-income countries is needed . Clinical Trials Registration NCT01375647 Background Salmonella Typhi is the major cause of enteric fever in lower-income countries . New conjugate vaccines show promise as public health interventions , but there are no efficacy data available from endemic areas . Methods Data were obtained from a previously published phase 3 r and omized controlled trial comparing Vi polysaccharide-tetanus toxoid conjugate vaccine ( Vi-TT ) with Vi polysaccharide vaccine ( Vi-PS )  in participants aged 2 - 45 years . An additional open-label arm administered Vi-TT to children aged 6 - 23 months . The proportion of participants with presumed clinical or sub clinical infection ( " seroincidence " ) was determined using mixture models and compared using relative risks ( RR 
    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 Immunologic development of soy-fed infants has not been extensively studied . Early studies of soy flour – based formulas showed decreased immunoglobulin production when soy protein intake was limited . However , there were no significant differences in rotavirus vaccine responses between breast-fed and soy protein isolate – based formula-fed infants .  Nucleotides added to milk-based formula benefit infant immune status , but reports of the immunologic effects of adding nucleotides to soy-based formula are not available . This study evaluated immune status and morbidity of infants fed soy protein isolate formulas with and without added nucleotides for 1 year . Methods Newborn , term infants enrolled in a masked 12-month feeding trial were assigned r and omly to groups fed soy formula with or without added nucleotides ( n = 94 , n = 92 ) . A nonr and omized human milk/formula cohort ( n = 81 ) was concurrently enrolled . Recommended immunizations were administered at 2 , 4 , and 6 months . Immune status was determined from antibody responses to Haemophilus influenzae type b , tetanus , diphtheria , and poliovirus vaccines at 6 , 7 , and 12 months . Parents and physicians reported morbidity data . Results All vaccine responses were within normal ranges . No response differences were observed between infants fed soy formula and those fed nucleotide-supplemented soy . However , antibody to H. influenzae type b at 7 and 12 months was higher in infants fed nucleotide-supplemented soy than in infants fed human milk/formula ( P = 0.007 , P = 0.008 , respectively ) . Human milk/formula-fed infants had higher poliovirus neutralizing antibody at 12 months than did soy-fed infants ( P = 0.016 ) . Morbidity analyses showed that only physician-reported diarrhea was different among groups ( groups fed human milk/formula had less diarrhea than did soy groups , P = 0.011 ) . Conclusions Term infants fed soy protein isolate – based formulas  have normal immune development as measured by antibody responses to childhood immunizations Background . Rotavirus ( RV ) is the leading cause of diarrhea-related death in children worldwide and 95 % of RV-associated deaths occur in Africa and Asia where RV vaccines ( RVVs ) have lower efficacy . We hypothesize that differences in intestinal microbiome composition correlate with the decreased RVV efficacy observed in poor setting s. Methods . We conducted a nested , case-control study comparing prevaccination , fecal microbiome compositions between 6-week old , matched RVV responders and nonresponders in rural Ghana . These infants ' microbiomes were then compared with 154 age-matched , healthy Dutch infants ' microbiomes , assumed to be RVV responders .  Fecal microbiome analysis was performed in all groups using the Human Intestinal Tract Chip . Results . We analyzed findings in 78 Ghanaian infants , including 39 RVV responder and nonresponder pairs . The overall microbiome composition was significantly different between RVV responders and nonresponders ( FDR , 0.12 ) , and Ghanaian responders were more similar to Dutch infants than nonresponders ( P = .002 ) . RVV response correlated with an increased abundance of Streptococcus bovis and a decreased abundance of the Bacteroidetes phylum in comparisons between both Ghanaian RVV responders and nonresponders ( FDR , 0.008 vs 0.003 ) and Dutch infants and Ghanaian nonresponders ( FDR , 0.002 vs 0.009 ) . Conclusions . The intestinal microbiome composition correlates significantly with RVV immunogenicity and may contribute to the diminished RVV immunogenicity observed in developing countries A vaccination trial , performed on 86 3-month-old infants , has shown that the ability of the RIT 4237 live attenuated rotavirus strain to induce seroconversion is dramatically reduced when administered with live poliovirus vaccine . In a subsequent trial performed on 93 infants the attempt to overcome the poliovirus interference by administering two doses of associated vaccines was unsuccessful . No interference by the RIT 4237 strain on live attenuated polioviruses was observed Background A strategy of administering a neonatal rotavirus vaccine at birth to target early prevention of rotavirus gastroenteritis may address some of the barriers to global implementation of a rotavirus vaccine . Methods We conducted a r and omized , double‐blind , placebo‐controlled trial in Indonesia to evaluate the efficacy of an oral human neonatal rotavirus vaccine ( RV3‐BB ) in preventing rotavirus gastroenteritis . Healthy newborns received three doses of RV3‐BB , administered according to a neonatal schedule ( 0 to 5 days , 8 weeks , and 14 weeks of age ) or an infant schedule ( 8 weeks , 14 weeks , and 18 weeks of age ) , or placebo . The primary analysis was conducted in the per‐ protocol population , which included only participants who received all four doses of vaccine or placebo within the visit windows , with secondary analyses performed in the intention‐to‐treat population , which included all participants who underwent r and omization . Results Among the 1513 participants in the per‐ protocol population , severe rotavirus gastroenteritis occurred up to the age of 18 months in 5.6 % of the participants in the placebo group ( 28 of 504 babies ) , in 1.4 % in the neonatal‐schedule vaccine group ( 7 of 498 ) , and in 2.7 % in the infant‐schedule vaccine group ( 14 of 511 ) . This result ed in a vaccine efficacy of 75 % ( 95 % confidence interval [ CI ] , 44 to 91 ) in the neonatal‐schedule group ( P<0.001 ) , 51 % ( 95 % CI , 7 to 76 ) in the infant‐schedule group ( P=0.03 ) , and 63 % ( 95 % CI , 34 to 80 ) in the neonatal‐schedule and infant‐schedule groups combined ( combined vaccine group ) ( P<0.001 ) . Similar results were observed in the intention‐to‐treat analysis ( 1649 participants ) ; the vaccine efficacy was 68 % ( 95 % CI , 35 to 86 ) in the neonatal‐schedule group ( P=0.001 ) , 52 % ( 95 % CI , 11 to 76 ) in the infant‐schedule group ( P=0.02 ) , and 60 % ( 95 % CI , 31 to 76 ) in the combined vaccine group ( P<0.001 ) . Vaccine response , as evidence d by serum immune response or shedding of RV3‐BB in the stool , occurred in 78 of 83 participants ( 94 % ) in the neonatal‐schedule group and in 83 of 84 participants ( 99 % ) in the infant‐schedule group . The incidence of adverse events was similar across the groups . No episodes of intussusception occurred within the 21‐day risk period after administration of any dose of vaccine or placebo , and one episode of intussusception occurred 114 days after the third dose of vaccine in the infant‐schedule group . Conclusions RV3‐BB was efficacious in preventing severe rotavirus gastroenteritis when administered according to a neonatal or an infant schedule in Indonesia . ( Funded by the Bill and Melinda Gates Foundation and others ; Australian New Zeal and Clinical Trials Registry number , ACTRN12612001282875 . BACKGROUND Oral poliovirus vaccine is less immunogenic and effective in low-income countries than in high-income countries , similarly to other oral vaccines . The high prevalence of intestinal pathogens and associated environmental enteropathy has been proposed to explain this problem . Because administration of an antibiotic has the potential to resolve environmental enteropathy and clear bacterial pathogens , we aim ed to assess whether antibiotics would improve oral poliovirus vaccine immunogenicity . METHODS We did a double-blind , r and omised , placebo-controlled trial of the effect of azithromycin on the immunogenicity of serotype-3 monovalent oral poliovirus vaccine given to healthy infants living in 14 blocks of Vellore district , India . Infants were eligible to participate if they were 6 - 11 months old , available for the study duration , and lacked serum neutralising antibodies to serotype-3 poliovirus . Infants were r and omly assigned ( 1:1 ) at enrolment to receive oral 10 mg/kg azithromycin or placebo once daily for 3 days , followed by serotype-3 monovalent oral poliovirus vaccine on day 14 . The primary outcome was detection of serum neutralising antibodies to serotype-3 poliovirus at a dilution of one in eight or more on day 35 and was assessed in the per- protocol population ( ie , all those who received azithromycin or placebo , oral poliovirus vaccine , and provided a blood sample according to the study protocol ) . Safety outcomes were assessed in all infants enrolled in the study . The trial is registered with the Clinical Trials Registry India , number CTRI/2014/05/004588 . FINDINGS Between Aug 5 , 2014 , and March 21 , 2015 , 754 infants were r and omly assigned : 376 to receive azithromycin and 378 to placebo . Of these , 348 ( 93 % ) of 376 in the azithromycin group and 357 ( 94 % ) of 378 infants in the placebo group completed the study per protocol . In the azithromycin group , 175 ( 50 % ) seroconverted to serotype-3 poliovirus compared with 192 ( 54 % ) in the placebo group ( risk ratio 0·94 , 95 % CI 0·81 - 1·08 ; p=0·366 ) . Azithromycin  reduced faecal biomarkers of environmental enteropathy ( calprotectin , myeloperoxidase , α1-antitrypsin ) and the prevalence of bacterial but not viral or eukaryotic pathogens . Viral pathogens were associated with lower seroconversion . Three serious adverse events were reported ( two in the azithromycin group and one in the placebo group ) , but none was considered related to the study interventions . INTERPRETATION Azithromycin did not improve the immunogenicity of oral poliovirus vaccine despite reducing biomarkers of environmental enteropathy and the prevalence of pathogenic intestinal bacteria . Viral interference and innate antiviral immune mechanisms might be more important determinants of the immunogenicity of live-virus oral vaccines . FUNDING Bill & Melinda Gates Foundation Abstract Background Rotavirus (RV)–specific immunoglobulin A ( IgA ) responses following oral RV vaccination are impaired in low-income countries , where the utility of RV-IgA as a correlate of protection ( CoP ) remains unclear . In a monovalent oral RV vaccine ( Rotarix ) efficacy trial among infants in Dhaka , Bangladesh , we identified factors associated with poor RV-IgA responses and explored the utility of RV-IgA as a CoP. Methods Infants were r and omized to receive Rotarix or no Rotarix at 10 and 17 weeks of life and followed with active diarrheal surveillance .  RV-IgA concentration , seroconversion , and seropositivity were determined at 18 weeks of life and analyzed for correlation(s ) with rotavirus diarrhea ( RVD ) and for contribution to Rotarix vaccine effect . Results Among vaccinated infants , overall RV-IgA geometric mean concentration was 21 U/mL ; only 27 % seroconverted and 32 % were seropositive after vaccination . Increased RV-specific maternal antibodies significantly impaired immunogenicity . Seroconversion was associated with reduced risk of RVD through 1 year of life , but RV-IgA seropositivity only explained 7.8 % of the vaccine effect demonstrated by the clinical endpoint ( RVD ) . Conclusions RV-IgA responses were low among infants in Bangladesh and were significantly impaired by maternal antibodies . RV-IgA is a suboptimal CoP in this setting ; an improved CoP for RV in low-income countries is needed . Clinical Trials Registration NCT01375647 Background Salmonella Typhi is the major cause of enteric fever in lower-income countries . New conjugate vaccines show promise as public health interventions , but there are no efficacy data available from endemic areas . Methods Data were obtained from a previously published phase 3 r and omized controlled trial comparing Vi polysaccharide-tetanus toxoid conjugate vaccine ( Vi-TT ) with Vi polysaccharide vaccine ( Vi-PS )  in participants aged 2 - 45 years . An additional open-label arm administered Vi-TT to children aged 6 - 23 months . The proportion of participants with presumed clinical or sub clinical infection ( " seroincidence " ) was determined using mixture models and compared using relative risks ( RR 
    Output:
    