Effect of concurrent viral infection on systemic and local antibody responses to live attenuated and enhanced-potency inactivated poliovirus vaccines. Effect of human rotavirus vaccine on severe diarrhea in African infants. The immunological response of Nigerian infants to attenuated and inactivated poliovaccines. Factors affecting the immunogenicity of oral poliovirus vaccine: a prospective evaluation in Brazil and the Gambia. World Health Organization Collaborative Study Group on Oral Poliovirus Vaccine. Safety and immunogenicity of different immunization regimens of CVD 103-HgR live oral cholera vaccine in soldiers and civilians in Thailand. Influence of host related factors on the antibody response to trivalent oral polio vaccine in Tunisian infants. Host and Viral Factors Affecting the Decreased Immunogenicity of Sabin Type 3 Vaccine after Administration of Trivalent Oral Polio Vaccine to Rural Mayan Children Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study
OBJECTIVE To determine the effect of an asymptomatic nonpolioviral infection on the immune response to poliovirus vaccines . DESIGN Open comparative trial . SETTING Well-child clinic at The Children 's Hospital of Buffalo , NY . PARTICIPANTS Twenty-seven healthy infants infected with nonpolioviruses and 27 healthy controls matched for age and vaccine group . INTERVENTIONS Trivalent oral attenuated poliovirus vaccine or enhanced potency inactivated vaccine administered at ages 4 and 12 months . MEASUREMENTS /MAIN RESULTS Neutralizing antibody to poliovirus serotypes 1 , 2 , and 3 were determined in the serum and nasopharyngeal secretion sample s obtained at ages 4 , 5 , 12 , and 13 months . The IgA antibody titers for polioviruses 1 , 2 , and 3 were measured in nasopharyngeal secretion sample s during the same periods . Antibody responses to poliovirus vaccines were similar in coinfected subjects and healthy controls at ages 5 and 13 months , except for serum neutralizing antibody that was significantly elevated in the controls compared with coinfected subjects ( geometric mean [ + /- SD ] antibody titers , 12.7 + /- 1.6 vs 11.5 + /- 1.7 ) . Concurrent viral infections affected the immune response in recipients of the oral poliovirus vaccine and the enhanced-potency inactivated poliovirus vaccine similarly . The immune response to polioviruses 1 and 3 were more adversely affected by coinfection than was the immune response to poliovirus 2 . CONCLUSION Concurrent asymptomatic viral infections minimally impaired the immune response to poliovirus vaccines . The adverse effects of coinfection were considered clinical ly insignificant BACKGROUND Rotavirus is the most common cause of severe gastroenteritis among young children worldwide . Data are needed to assess the efficacy of the rotavirus vaccine in African children . METHODS We conducted a r and omized , placebo-controlled , multicenter trial in South Africa ( 3166 infants ; 64.1 % of the total ) and Malawi ( 1773 infants ; 35.9 % of the total ) to evaluate the efficacy of a live , oral rotavirus vaccine in preventing severe rotavirus gastroenteritis . Healthy infants were r and omly assigned in a 1:1:1 ratio to receive two doses of vaccine ( in addition to one dose of placebo ) or three doses of vaccine - the pooled vaccine group - or three doses of placebo at 6 , 10 , and 14 weeks of age . Episodes of gastroenteritis caused by wild-type rotavirus during the first year of life were assessed through active follow-up surveillance and were grade d with the use of the Vesikari scale . RESULTS A total of 4939 infants were enrolled and r and omly assigned to one of the three groups ; 1647 infants received two doses of the vaccine , 1651 infants received three doses of the vaccine , and 1641 received placebo . Of the 4417 infants included in the per- protocol efficacy analysis , severe rotavirus gastroenteritis occurred in 4.9 % of the infants in the placebo group and in 1.9 % of those in the pooled vaccine group ( vaccine efficacy , 61.2 % ; 95 % confidence interval , 44.0 to 73.2 ) . Vaccine efficacy was lower in Malawi than in South Africa ( 49.4 % vs. 76.9 % ) ; however , the number of episodes of severe rotavirus gastroenteritis that were prevented was greater in Malawi than in South Africa ( 6.7 vs. 4.2 cases prevented per 100 infants vaccinated per year ) . Efficacy against all-cause severe gastroenteritis was 30.2 % . At least one serious adverse event was reported in 9.7 % of the infants in the pooled vaccine group and in 11.5 % of the infants in the placebo group . CONCLUSIONS Human rotavirus vaccine significantly reduced the incidence of severe rotavirus gastroenteritis among African infants during the first year of life . ( Clinical Trials.gov number , NCT00241644 . ) A comparison was made of the immunity conferred by injected formalin-killed poliomyelitis vaccine and orally administered attenuated poliomyelitis vaccine in Nigerian infants under tropical conditions where interfering enteroviruses have caused poor conversion rates with attenuated poliomyelitis vaccine . Two hundred and thirty infants completed the immunization schedules . The levels of antibodies to polioviruses were assessed before immunization and at periodic intervals during the trial . Seventy-four per cent , 72 % and 85 % of the children lacked antibodies to poliovirus types 1 , 2 and 3 respectively at 6 months if they received no vaccine , the comparative proportions respectively were 52 % , 8 % and 48 % if they had oral attenuated poliovaccine and 2 % , 4 % and 0 % if they had three doses of inactivated poliovaccine . It is suggested that killed poliovaccine incorporated in a quadruple vaccine may have a place in developing countries like Nigeria in the control of diphtheria , tetanus , whooping cough and poliomyelitis To assess factors that may influence the immunogenicity of oral poliovirus vaccine ( OPV ) , neutralizing antibody responses were measured in 1409 infants in Brazil and the Gambia who were r and omized to receive one of four different formulations of OPV at approximately birth and at 6 , 10 , and 14 weeks .  Overall seroconversion rates at the end of the trial were 85 % for poliovirus type 1 ( P1 ) , 94 % for type 2 ( P2 ) , and 68 % for type 3 ( P3 ) . Factors associated with vaccine failure included high levels of maternal antibody ( P1 , P2 , and P3 ) , vaccination during the rainy season ( P1 , P2 , and P3 ) , diarrhea at the time of vaccination ( P2 and P3 ) , household exposure to other OPV recipients ( P1 ) , and breast-feeding ( P3 ) ( P < .05 for each factor , logistic regression analysis ) . OPV containing twice the st and ard potency of Sabin type 1 virus increased seroconversion rates to P1 by 8 % in Brazil ( P < .05 ) and 15 % in the Gambia ( P < .001 ) . Suboptimal responses to OPV in developing countries are determined by a complex array of factors related to the vaccine , host , and environment Attenuated Vibrio cholerae oral vaccine CVD 103-HgR was well tolerated by 324 Thai soldiers and civilians . Most received a single 5 x 10(8 ) cfu dose , while 40 each received one or two 5 x 10(9 ) cfu doses . Vibriocidal antibody ( the best correlate of immunity ) seroconversion was lower in soldiers than civilians ( P less than .001 ) . Increasing the vaccine dose to 5 x 10(9 ) cfu raised the geometric mean titer ( P less than .001 ) . A second 5 x 10(9 ) cfu dose one week later did not notably increase seroconversions . Likelihood of seroconversion was inversely correlated with baseline vibriocidal titer ( P less than .001 ) . CVD 103-HgR caused seroconversion in most subjects with baseline titers less than or equal to 1:40 , including 100 % of civilians after one 5 x 10(8 ) cfu dose , 79 % of soldiers after one 5 x 10(9 ) cfu dose , and 45 % of soldiers after one 5 x 10(8 ) cfu dose . In persons with elevated baseline titers , vibriocidal antibody seroconversion is not a sensitive measure of whether vaccine has boosted intestinal immunity ; for such subjects , other measurements must be used . Study regimens in endemic areas should use a single 5 x 10(9 ) cfu dose The low efficiency of trivalent oral polio vaccine ( TOPV ) in inducing protective antibody titres to polio3 is a problem of great importance in many regions of the world . A prospect i ve study was conducted in 121 Tunisian infants aged 3 months during routine immunization with TOPV under carefully controlled conditions .  Seroconversion rates to  polio1 , polio2 and polio3  , one month after the third dose , were 94.7 , 100 and 89.5 % , respectively . The kinetics of the antibody response showed delayed and more difficult responses to polio3 compared to polio2 and polio1 . The following host related factors , previously suggested to interfere with the immune response , were assessed : maternal antibodies ; breast-feeding ; concurrent enteric infections ; and other illnesses . The main factor associated with the lack of seroconversion was concurrent infection with non-polio enteroviruses ( NPE ) which was found in 50 % of non-responders to polio1 and /or to polio3 during the vaccination protocol whereas no NPE was isolated in vaccine responders . The other studied factors seemed not to interfere in the infants according to the locally adopted vaccination schedule and to the specific socio-economic conditions Abstract Factors affecting immunogenicity of the first 2 doses of oral poliovirus vaccine ( OPV ) among unimmunized Mayan infants were prospect ively evaluated . The relative impact of multiple variables , including mass or routine vaccination , concurrent enteric bacterial ( salmonella , shigella , and campylobacter ) and viral ( adenovirus 40/41 , astrovirus , nonpolio enteroviruses , and rotavirus ) infections , interference among Sabin vaccine viruses , and preexisting poliovirus antibodies were studied . Sera were available from 181 infants after 2 OPV doses .  Seroresponses were 86 % to Sabin type 1 , 97 % to Sabin type 2 , and 61 % to Sabin type 3 vaccines . Mass versus routine vaccination and preexisting poliovirus antibodies did not affect immunogenicity . By multiple logistic regression analysis , fecal shedding of homologous Sabin strains was associated with increased seroresponses to all Sabin types , especially to Sabin type 3 . Decreased  OPV immunogenicity was primarily attributable to interference of Sabin type 3 by Sabin type 2 . OPV formulations with higher doses of Sabin type 3 could improve immunogenicity among infants in developing countries BACKGROUND Diarrhoeal diseases cause illness and death among children younger than 5 years in low-income countries . We design ed the Global Enteric Multicenter Study ( GEMS ) to identify the aetiology and population -based burden of paediatric diarrhoeal disease in sub-Saharan Africa and south Asia . METHODS The GEMS is a 3-year , prospect i ve , age-stratified , matched case-control study of moderate-to-severe diarrhoea in children aged 0 - 59 months residing in censused population s at four sites in Africa and three in Asia . We recruited children with moderate-to-severe diarrhoea seeking care at health centres along with one to three r and omly selected matched community control children without diarrhoea . From patients with moderate-to-severe diarrhoea and controls , we obtained clinical and epidemiological data , anthropometric measurements , and a faecal sample to identify enteropathogens at enrolment ; one follow-up home visit was made about 60 days later to ascertain vital status , clinical outcome , and interval growth . FINDINGS We enrolled 9439 children with moderate-to-severe diarrhoea and 13,129 control children without diarrhoea . By analysing adjusted population attributable fractions , most attributable cases of moderate-to-severe diarrhoea were due to four pathogens : rotavirus , Cryptosporidium , enterotoxigenic Escherichia coli producing heat-stable toxin ( ST-ETEC ; with or without co-expression of heat-labile enterotoxin ) , and Shigella . Other pathogens were important in selected sites ( eg , Aeromonas , Vibrio cholerae O1 , Campylobacter jejuni ) . Odds of dying during follow-up were 8·5-fold higher in patients with moderate-to-severe diarrhoea than in controls ( odd ratio 8·5 , 95 % CI 5·8 - 12·5 , p<0·0001 ) ; most deaths ( 167 [ 87·9 % ] ) occurred during the first 2 years of life . Pathogens associated with increased risk of case death were ST-ETEC ( hazard ratio [ HR ] 1·9 ; 0·99 - 3·5 ) and typical enteropathogenic E coli ( HR 2·6 ; 1·6 - 4·1 ) in infants aged 0 - 11 months , and Cryptosporidium ( HR 2·3 ; 1·3 - 4·3 ) in toddlers aged 12 - 23 months . INTERPRETATION Interventions targeting five pathogens ( rotavirus , Shigella , ST-ETEC , Cryptosporidium , typical enteropathogenic E coli ) can substantially reduce the burden of moderate-to-severe diarrhoea . New methods and accelerated implementation of existing interventions ( rotavirus vaccine and zinc ) are needed to prevent disease and improve outcomes . FUNDING The Bill & Melinda Gates Foundation
BACKGROUND The impaired immunogenicity of  oral poliovirus vaccine ( OPV ) in low-income countries has been apparent since the early field trials of this vaccine .
Infection with enteropathogens at the time of vaccination may contribute to this phenomenon .
However , the relative influence of these infections on OPV performance remains uncertain .
METHODS We conducted a systematic review to examine the impact of concurrent enteric infections on OPV response .