Immune responses in Vietnamese children after a single dose of the auxotrophic, live Shigella flexneri Y vaccine strain SFL124. Safety, dose, immunogenicity, and transmissibility of an oral live attenuated Shigella flexneri 2a vaccine candidate (SC602) among healthy adults and school children in Matlab, Bangladesh. Oral, inactivated, whole cell enterotoxigenic Escherichia coli plus cholera toxin B subunit vaccine: results of the initial evaluation in children. PRIDE Study Group. Private demand for cholera vaccines in Beira, Mozambique. Safety, immunogenicity, and transmissibility of single-dose live oral cholera vaccine strain CVD 103-HgR in 24- to 59-month-old Indonesian children. Safety and immunogenicity of an oral, inactivated enterotoxigenic Escherichia coli plus cholera toxin B subunit vaccine in Bangladeshi children 18-36 months of age. Efficacy of a Low-Cost, Inactivated Whole-Cell Oral Cholera Vaccine: Results from 3 Years of Follow-Up of a Randomized, Controlled Trial Safety and immunogenicity of oral killed whole cell recombinant B subunit cholera vaccine in Barranquilla, Colombia. Evaluation of a probiotics, Bifidobacterium breve BBG-01, for enhancement of immunogenicity of an oral inactivated cholera vaccine and safety: a randomized, double-blind, placebo-controlled trial in Bangladeshi children under 5 years of age. Safety and immunogenicity of Shigella sonnei-CRM9 and Shigella flexneri type 2a-r EPAsucc conjugate vaccines in one- to four-year-old children Efficacy trial of single-dose live oral cholera vaccine CVD 103-HgR in North Jakarta, Indonesia, a cholera-endemic area. Field trial of inactivated oral cholera vaccines in Bangladesh: results from 5 years of follow-up. Palatability, reactogenicity and immunogenicity of engineered live oral cholera vaccine CVD 103-HgR in Chilean infants and toddlers. Safety, immunogenicity, and lot stability of the whole cell/recombinant B subunit (WC/rCTB) cholera vaccine in Peruvian adults and children. Shigella flexneri 2a and sonnei I vaccine with two attenuating markers: construction, tolerability and immunogenicity in 143 children aged 3-17 years. Peru-15, a live attenuated oral cholera vaccine, is safe and immunogenic in Bangladeshi toddlers and infants. Efficacy of pentavalent rotavirus vaccine against severe rotavirus gastroenteritis in infants in developing countries in Asia: a randomised, double-blind, placebo-controlled trial Safety and immunogenicity of Shigella sonnei and Shigella flexneri 2a O-specific polysaccharide conjugates in children. Introductory evaluation of an oral, killed whole cell enterotoxigenic Escherichia coli plus cholera toxin B subunit vaccine in Egyptian infants Studies on vaccination against bacillary dysentery. 6. Protection of children by oral immunization with streptomycin-dependent Shigella strains. Field trial of a locally produced, killed, oral cholera vaccine in Vietnam Efficacy of pentavalent rotavirus vaccine against severe rotavirus gastroenteritis in infants in developing countries in sub-Saharan Africa: a randomised, double-blind, placebo-controlled trial Safety and efficacy of human rotavirus vaccine during the first 2 years of life in Asian infants: randomised, double-blind, controlled study. Age-related efficacy of Shigella O-specific polysaccharide conjugates in 1-4-year-old Israeli children.
The live , auxotrophic Shigella flexneri vaccine strain SFL124 was given in a single dose of 10(7 ) , 10(8 ) or 10(9 ) colony forming units ( cfu ) , respectively , to each of three groups of 10 Vietnamese children aged 9 - 14 years . The vaccine was well tolerated by all the children without any severe side effects such as diarrhoea or fever being observed . Mild symptoms were reported by five children . Only five children were found by culture to excrete SFL124 but , by PCR , 28 of 30 children were found to excrete the vaccine strain for up to 5 days ( mean 2.8 days ) with insignificant differences among the groups . Local mucosal immune responses and antibody secreting cell ( ASC ) responses to S. flexneri lipopolysaccharide ( LPS ) and invasion plasmid-coded antigens ( Ipa ) were elicited in the children in a dose-dependent manner . Doses of 10(9 ) cfu induced most prominent responses , followed by those of 10(8 ) and 10(7 ) cfu . The sIgA responses were the highest whereas the ASC were modest . High titres of serum antibodies to Shigella LPS and Ipa were found in all the children before ingestion of the vaccine which elicited increases in serum antibody titres in only a few of them . The immune response patterns seen indicate a booster rather than a primary response and may be a consequence of the endemic nature of shigellosis in Vietnam In double-blind trials in Bangladesh , 88 adults , and 79 children ( 8 - 10 years ) were r and omized to receive either a single oral dose of 1 × 10(4 ) , 1 × 10(5 ) or 1 × 10(6)CFU of SC602 ( a live , attenuated Shigella flexneri 2a strain vaccine ) or placebo . In the adult outpatient 1 × 10(6 ) CFU group , severe joint pain and body aches were reported by one and two vaccinees respectively . In the adult inpatient trial , SC602 was isolated from 3 volunteers , pre-vaccination antibody titers were high , and fourfold increases in serum IgG anti-LPS responses were observed in 2 of 5 subjects of the 1 × 10(6)CFU group . None of the volunteers developed diarrhea . Overall , SC602 was found to be associated with minimal vaccine shedding , minimal reactogenicity , no transmission risk , and low immune stimulation Two r and omized , double-blinded trials assessed the safety and immunogenicity of an oral , killed enterotoxigenic Escherichia coli ( ETEC ) plus cholera toxin B subunit vaccine in Egyptian children . Two doses of vaccine or E. coli K-12 were given 2 weeks apart to 105 6- to 12-year-olds and 97 2- to 5-year-olds .  Safety was monitored for 3 days after each dose . Blood was collected before immunization and 7 days after each dose to measure immune responses . Few children reported postdosing symptoms , with no differences in the frequency of symptoms between treatment groups . Most vaccinees had an IgA antibody-secreting cell response against colonization factor antigen I ( 100 % , 6 - 12 years ; 95 % , 2 - 5 years ) , coli surface antigen 2 ( 92 % , 6 - 12 years ; 83 % , 2 - 5 years ) , and coli surface antigen 4 ( 93 % , 6 - 12 years ) . Vaccination evoked a > /=4-fold rise in antitoxic IgA and IgG titers in 93 % and 81 % of children , respectively . In conclusion , the oral ETEC vaccine was safe and immunogenic in 2- to 12-year-old children , justifying further evaluation in infants In the summer of 2005 , we interviewed 996 r and omly selected respondents in Beira , Mozambique concerning their willingness and ability to pay for cholera vaccine for themselves and for other household members . Respondents were told that two doses of the vaccine would be required 2 weeks apart , and that the cholera vaccine would offer excellent protection against infection for the first year following vaccination , and some protection during the second and third year after a person is vaccinated . This research was carried out in order to learn more about private dem and for vaccines in a cholera-endemic area . We asked two types of valuation questions : ( 1 ) a discrete-price offer for a vaccine that could be purchased for household members and ( 2 ) a payment card design ed to assess uncertainty in the respondent 's dem and for a vaccine for self-protection . We estimate average household willingness to pay ( WTP ) for cholera vaccines in Beira to be 2005 US$ 8.45 . This estimate of household WTP represents the perceived private economic benefits to a household -- six persons on average -- of giving all members free cholera vaccines Recombinant A-B+ Vibrio cholerae O1 strain CVD 103-HgR is a safe , highly immunogenic , single-dose live oral vaccine in adults in industrialized countries .  Safety , excretion , immunogenicity , vaccine transmissibility , and environmental introduction of CVD 103-HgR were investigated among 24- to 59-month-old children in Jakarta . In 81 households , 1 child was r and omly allocated a single dose of vaccine ( 5 x 10(9 ) cfu ) and another , placebo . Additionally , 139 unpaired children were r and omly allocated vaccine or placebo .  During 9 days of follow-up , diarrhea or vomiting did not occur more often among vaccines than controls . Vaccine was minimally excreted and was isolated from no controls and from 1 ( 0.6 % ) of 177 unvaccinated family contacts . A 4-fold or higher rise in serum vibriocidal antibody was observed in 75 % of vaccines ( 10-fold rise in geometric mean titer over baseline ) . Of 135 paired placebo recipients or household contacts , 5 had vibriocidal seroconversions . Moore swabs placed in sewers and latrines near 97 households failed to detect vaccine . These observations pave the way for a large-scale field trial of efficacy A phase II safety and immunogenicity study of an oral-formalin inactivated enterotoxigenic Escherichia coli ( ETEC ) vaccine containing six colonization factors ( CFA/I , CS1 , CS2 , CS3 , CS4 , CS5 ) and 1 mg of recombinant cholera toxin B subunit ( the CF-BS-ETEC vaccine ) was carried out in an urban slum of Dhaka city in Bangladesh . The study was carried out in a double blinded , placebo controlled design in 158 children , 18 - 36 months of age . Children were given two doses of the CF-BS-ETEC vaccine or the placebo which consisted of E. coli K12 . The vaccine was well tolerated . The immune response was studied in 60 children ( 30 each in the placebo and vaccine group ) . Significant vaccine specific IgA antibody-secreting cell ( ASC ) responses were seen 7 days after ingestion of the first and second dose of the vaccine . The responses to CFA/I ( P < or=0.001 ) , CS2 ( P=0.021 ) , CS4 ( P=0.009 ) and rCT B ( P < or=0.001 ) were elevated in the vaccines in comparison to the pre-immune values and in comparison to those seen in the placebo recipients ( P=0.018 to < 0.001 ) . Vaccines but not placebo recipients also showed significantly increased IgM ASC responses to all three CF antigens that were tested ( P=0.012 to < 0.001 ) and IgG-ASCs to rCT B ( P<0.001 ) . Peak ASC levels were reached after one dose of the vaccine with no further increase or decrease after the second dose . The vaccine recipients also responded with IgA plasma antibodies to CFA/I , CS1 , CS2 , CS4 and rCT B after one or two doses of the vaccine ( P=0.01 to < 0.001 ) . Subjects in the placebo group failed to mount responses to any of the antigens . The vaccine also induced responses in mucosal IgA antibodies in feces to CFA/I , CS2 and rCT B ( 61 , 88 and 69 % responder frequency , respectively ) and the magnitude of the response was elevated in comparison to the pre-immune levels ( P=0.031 to < 0.001 ) and to the levels of the control group ( P=0.003 to < 0.001 ) . This study thus shows that the CF-BS-ETEC vaccine is well tolerated in children , 18 - 36 months of age and gives rise to significant systemic and mucosal IgA antibody responses Background Killed oral cholera vaccines ( OCVs ) have been licensed for use in developing countries , but protection conferred by licensed OCVs beyond two years of follow-up has not been demonstrated in r and omized , clinical trials . Methods /Principal Findings We conducted a cluster-r and omized , placebo-controlled trial of a two-dose regimen of a low-cost killed whole cell OCV in residents 1 year of age and older living in 3,933 clusters in Kolkata , India . The primary endpoint was culture-proven Vibrio cholerae O1 diarrhea episodes severe enough to require treatment in a health care facility . Of the 66,900 fully dosed individuals ( 31,932 vaccinees and 34,968 placebo recipients ) , 38 vaccinees and 128 placebo-recipients developed cholera during three years of follow-up ( protective efficacy 66 % ; one-sided 95%CI lower bound = 53 % , p<0.001 ) . Vaccine protection during the third year of follow-up was 65 % ( one-sided 95%CI lower bound = 44 % , p<0.001 ) . Significant protection was evident in the second year of follow-up in children vaccinated at ages 1–4 years and in the third year in older age groups . Conclusions / Significance The killed whole-cell OCV conferred significant protection that was evident in the second year of follow-up in young children and was sustained for at least three years in older age groups . Continued follow-up will be important to establish the vaccine 's duration of protection . Trial Registration Clinical Trials.gov NCT00289224 In January and February 1992 , an assessment was conducted of the safety and immunogenicity of two doses of a new oral cholera vaccine prepared from the recombinant B subunit of the toxin and from killed whole cells ( rBS/WC ) in 1,165 individuals between the ages of 12 months and 64 years in Barranquilla , Colombia . This was a r and omized , double-blind placebo-controlled study . Participants received two doses of either the vaccine or a placebo ( killed Escherichia coli K12 ) over a two-week interval . Few symptoms were detected during the three days following administration of the initial dose and even fewer following the second . Sera obtained upon administration of the first dose and two weeks after administration of the second were tested for Vibrio cholerae 01 Inaba vibriocidal antibodies and antitoxins . Geometric mean titers ( GMT ) of vibriocidal antibodies were found to increase two-fold in subjects receiving the vaccine . In the paired sample s taken from vaccinated subjects , two-fold or greater increases were observed in 44 % and four-fold or greater increases were observed in 34 % , as compared to similar increases in 9.2 % and 2.2 % of the sera taken from those receiving the placebo ( P < 0.05 ) . The GMTs of IgG and IgA antitoxins , as determined by ELISA , increased by factors of 4 and 3.2 , respectively , in those receiving the vaccine , as compared to factors of 1.1 and 1.1 in those given the placebo ( P < 0.001 for IgG , P < 0.01 for IgA ) . Approximately 80 % of the paired sample s from the vaccinated group showed an increase of both IgG and IgA antitoxins > or = 1.5 , as compared to only about 20 % of those in the placebo group ( P < 0.000001 ) . Belonging to the O blood group did not significantly affect the immune response . Children under age four tended to show a weaker vibriocidal antibody response and a stronger antitoxin response than older subjects . The two doses of oral vaccine were found to be safe and without attributable side-effects . The vibriocidal antibody and antitoxin responses were similar to those obtained previously with the conventional oral killed whole cell B subunit cholera vaccine To evaluate the probiotic , Bifidobacterium breve strain Yakult ( BBG-01 ) , for safety and enhancement of immunogenicity in an oral inactivated cholera vaccine , a r and omized double-blind placebo-controlled study was performed . Bangladeshi children under 5-year-old received BBG-01 or placebo for 4 weeks with two doses of oral cholera vaccine .  Serum/fecal antibodies and fecal bacterial flora in the study participants were monitored . All adverse events were mild and transient and had no significant difference between the two groups . Immunological responses were similar comparing the two groups . A negative correlation between Bifidobacterium and Enterobacteriaceae in the probiotic group suggests a possible involvement of BBG-01 in alteration of the enteric bacterial flora . In conclusion , BBG-01 is well tolerated by Bangladeshi children although the post vaccinal immunostimulatory effect of BBG-01 was not evident Background and objective . Shigella conjugate vaccines have been shown to be safe , immunogenic and efficacious in adult volunteers . We have now investigated the safety and immunogenicity of investigational Shigella sonnei and Shigella flexneri 2a conjugate vaccines in 1- to 4-year-old children , the age group at greatest risk for shigellosis . Methods . The O-specific polysaccharides of S. sonnei and S. flexneri 2a , the two most common shigellae from patients in Israel , were bound to medically useful carrier proteins to form conjugates . Eighty healthy 1- to 4-year-olds were r and omized to receive two 0.5-ml i m injections 6 weeks apart of either S. sonnei-CRM9 or S. flexneri 2a-r EPAsucc . Blood was taken before , 6 weeks after the first injection , 4 weeks after the second injections and 2 years after immunization for assay of IgG anti-lipopolysaccharide , diphtheria toxin and Pseudomonas aeruginosa exotoxin A antibodies by enzyme-linked immunosorbent assay . Results . During an 8-day surveillance period after each immunization , low fever ( 37.8–39.0 ° C ) lasting only 24 to 48 h occurred in 2 of 40 recipients after the first injection and 4 of 40 recipients after the second injection of S. flexneri 2a-r EPAsucc and in 2 of 38 of S. sonnei-CRM9 after the second injection ; no fever was detected after the first injection . Liver function tests were normal in all vaccinees . S. sonnei-CRM9 elicited a > 4-fold rise in IgG anti-LPS in 92.1 % and S. flexneri 2a-r EPAsucc in 85 % ( P < 0.0001 ) after the second injection ; both conjugates elicited type-specific booster responses . At 2 years the geometric mean concentrations of both IgG anti-lipopolysaccharides were significantly higher than preimmunization levels . A > 4-fold rise of IgG anti-diphtheria ( 65.8 % ) and IgG anti-ETA ( 77.5 % ) was observed . Conclusion . These experimental Shigella conjugate vaccines were safe and immunogenic in 1- to 4-year-old children A r and omized , double-blind , placebo-controlled efficacy trial of one dose of CVD 103-HgR live oral cholera vaccine was performed in Indonesia from 1993 to 1997 . 67,508 persons aged 2 - 41 years ingested vaccine or placebo and were followed for four years , detecting cholera cases using hospital-based surveillance . A nested reactogenicity study ( 538 vaccinees , 535 controls ) revealed no vaccine-attributable side effects . A nested immunogenicity study ( N=657 ) showed vibriocidal seroresponses in 64 - 70 % of vaccinees vs 1 - 2 % of controls . Cholera incidence was lower than expected . 103 cases of Vibrio cholerae O1 El Tor diarrhea were detected , 93 evaluable for vaccine efficacy ( 43 vaccine , 50 placebo ; efficacy=14 % ) . A suggestion of protection was observed among persons with blood group O [ P=0.12 ] . Only seven cases occurred within six months of vaccination , precluding assessment of short-term efficacy . In Jakarta , single-dose CVD 103-HgR did not confer long-term protection . Short-term protection from a single-dose and long-term protection from two doses have yet to be studied To determine the protective efficacy ( PE ) of three doses of oral B subunit-killed whole cell ( BS-WC ) or killed whole cell-only ( WC ) vaccines against cholera , a clinical trial was conducted among 62285 children over 2 years and adult women in rural Bangladesh . During 5 years of follow-up , there were 144 cases of cholera in the BS-WC group ( PE = 49 % ; P < 0.001 ) , 150 in the WC group ( PE = 47 % ; P < 0.001 ) , and 283 in the K12 group . Protection by each vaccine was evident only during the first three years of follow-up ; long-term protection of young children was observed only against classical but not El Tor cholera ; 3-year protection against both cholera biotypes occurred among older persons , but at a higher level against classical cholera BACKGROUND Live oral cholera vaccine CVD 103-HgR is well-tolerated and immunogenic when administered to adults , school age children and preschool children in a single 5 x 10(9 ) colony-forming unit dose . Because elicitation of immune responses after administration of a single dose is exceptional for any oral vaccine in any age group , CVD 103-HgR was used as a probe to investigate the clinical acceptability , practicality and immunogenicity of this vaccine in infants and toddlers 3 to 17 months of age . METHODS The study was undertaken successively in 12- to 17-month-olds ( n = 104 ) , 7- to 11-month-olds ( n = 106 ) and 3- to 5-month-olds ( n = 102 ) . One-half of the subjects were r and omly allocated to receive vaccine and the other one-half to receive placebo , in double blind fashion . After 2 weeks of double blind follow-up , all subjects received a dose of vaccine .  Vibriocidal antibody titers were measured on coded sera collected at baseline and 2 weeks after each dosing . The buffered vaccine " cocktail " had a volume of 100 ml ; subjects who ingested > or = 70 ml were considered fully vaccinated . FINDINGS Only 37 % of subjects overall ( 25 % of 3- to 5-month-olds ) ingested > or = 70 ml of the cocktail . The vaccine was well-tolerated with no significant differences in the rate or severity of adverse reactions after ingestion of vaccine vs. placebo . Seroconversion after ingestion of a single dose of CVD 103-HgR was similar in fully vaccinated subjects ( 66 % ) and in those who ingested a smaller fraction of the vaccine cocktail ( 63 % ) . Of subjects who ingested two doses , 5 of 118 excreted vaccine organisms on Day 7 after the first dose vs. 0 of 118 after the second dose . INTERPRETATION Single dose oral CVD 103-HgR is well-tolerated and immunogenic in infants even when a partial dose is ingested . The buffered vaccine cocktail that is readily imbibed by older children is not appealing to young infants , and improved vaccine formulations and delivery vehicles for immunizing infants must be sought To assess the safety , immunogenicity , and lot stability of the whole cell/recombinant B subunit cholera vaccine , 2 lots manufactured in June 1991 and February 1992 were tested in January 1995 . Two oral doses of vaccine or placebo given 2 weeks apart were given with buffer to 216 Peruvian adults and children . Symptoms were elicited for 3 days after each dose . Serum and plasma specimens obtained from each volunteer before vaccination and 10 - 14 days after the second dose were tested for vibriocidal and anti-cholera toxin antibodies . The vaccine was well-tolerated . Nearly half of the 100 vaccinees had pre-vaccination vibriocidal titers > or = 1:40 . Elevated titers were observed in 22 % of 37 children 2 - 5 years of age compared with 66 % of 63 vaccinees 6 - 65 years ( P < 0.001 ) . A > or = 2-fold serum vibriocidal response was observed in 55 % of 100 vaccinees and 6 % of 32 placebo recipients . An elevated pre-vaccination titer ( < or = 1:40 ) did not change the proportion of vaccinees who responded with a > or = 2-fold increase in vibriocidal titer ( 51 % versus 59 % , difference not significant ) , but did change the proportion responding with a > or = 4-fold increase ( 41 % versus 22 % ; P < 0.05 ) . The vibriocidal seroconversion rate was lowest in children 2 - 5 years old despite low pre-vaccination titers . Two-fold or greater serum antitoxic responses in IgA and IgG were observed in > 90 % of the vaccinees ; > or = 4-fold responses were seen in 65 - 70 % of the vaccinees with a 6 - 8-fold increase over baseline . Plasma specimens were as good as sera for determining anti-toxic antibodies by ELISA , but were less satisfactory for determining vibriocidal antibody titers The vaccine c and i date s were constructed through stepwise incorporation of weakly attenuated purine auxotrophy with subsequent rifampicin resistance ( RNA polymerase ) mutation to yield optimal attenuation . These strains showed a maintained invasiveness for conjunctival epithelia . Therefore , while not causing keratoconjunctivitis , they were excreted for a short but marked period and provided partial protection in the Sereny test . Children tolerated the maximum dose of 1 - 3 x 10(9 ) colony-forming units ( c.f.u . ) of lyophilized vaccine without side effects . This total dose distributed among three oral inoculations , induced coproantibodies in 70 % of recipients during the first three months . However , the single application of this total dose for primary immunization or booster proved to be more efficient : 90 % of the subjects had markedly elevated titres for not less than six months A live oral Vibrio cholerae O1 El Tor vaccine , Peru-15 was tested in a double-blind , r and omized placebo controlled study for safety and immunogenicity in Phase I and Phase II studies in 240 Bangladeshi children aged 9 months-5 years of age . Two different doses ( 2x10(7 ) and 2x10(8)cfu ) were tested . Vaccination did not elicit adverse events and the strain was genetically stable . Vibriocidal antibody responses developed in 42/50 ( 84 % ) toddlers ( 2 - 5 years ) and 35/50 ( 70 % ) of younger children ( 9 - 23 months ) and overall 77/100 ( 77 % ) who received the high dose . LPS-IgA-antibody responses were seen in 60 % of toddlers and 34 % of infants ; 40 % responded with IgA antibodies to cholera toxin . The responses to the reduced dose was lower . These studies demonstrate that Peru-15 at a dose of 2x10(8)cfu is safe and immunogenic in children in Bangladesh BACKGROUND Rotavirus vaccine has proved effective for prevention of severe rotavirus gastroenteritis in infants in developed countries , but no efficacy studies have been done in developing countries in Asia . We assessed the clinical efficacy of live oral pentavalent rotavirus vaccine for prevention of severe rotavirus gastroenteritis in infants in Bangladesh and Vietnam . METHODS In this multicentre , double-blind , placebo-controlled trial , undertaken in rural Matlab , Bangladesh , and urban and periurban Nha Trang , Vietnam , infants aged 4 - 12 weeks without symptoms of gastrointestinal disorders were r and omly assigned ( 1:1 ) to receive three oral doses of pentavalent rotavirus vaccine 2 mL or placebo at around 6 weeks , 10 weeks , and 14 weeks of age , in conjunction with routine infant vaccines including oral poliovirus vaccine . R and omisation was done by computer-generated r and omisation sequence in blocks of six . Episodes of gastroenteritis in infants who presented to study medical facilities were reported by clinical staff and from parent re collection . The primary endpoint was severe rotavirus gastroenteritis ( Vesikari score > or=11 ) arising 14 days or more after the third dose of placebo or vaccine to end of study ( March 31 , 2009 ; around 21 months of age ) . Analysis was per protocol ; infants who received scheduled doses of vaccine or placebo without intervening laboratory-confirmed naturally occurring rotavirus disease earlier than 14 days after the third dose and had complete clinical and laboratory results were included in the analysis . This study is registered with Clinical Trials.gov , number NCT00362648 . FINDINGS 2036 infants were r and omly assigned to receive pentavalent rotavirus vaccine ( n=1018 ) or placebo ( n=1018 ) . 991 infants assigned to pentavalent rotavirus vaccine and 978 assigned to placebo were included in the per- protocol analysis . Median follow up from 14 days after the third dose of placebo or vaccine until final disposition was 498 days ( IQR 480 - 575 ) . 38 cases of severe rotavirus gastroenteritis ( Vesikari score > or=11 ) were reported during more than 1197 person-years of follow up in the vaccine group , compared with 71 cases in more than 1156 person years in the placebo group , result ing in a vaccine efficacy of 48.3 % ( 95 % CI 22.3 - 66.1 ) against severe disease ( p=0.0005 for efficacy > 0 % ) during nearly 2 years of follow-up . 25 ( 2.5 % ) of 1017 infants assigned to receive vaccine and 20 ( 2.0 % ) of 1018 assigned to receive placebo had a serious adverse event within 14 days of any dose . The most frequent serious adverse event was pneumonia ( vaccine 12 [ 1.2 % ] ; placebo 15 [ 1.5 % ] ) . INTERPRETATION In infants in developing countries in Asia , pentavalent rotavirus vaccine is safe and efficacious against severe rotavirus gastroenteritis , and our results support exp and ed WHO recommendations to promote its global use . FUNDING PATH ( GAVI Alliance grant ) and Merck O-specific polysaccharide conjugates of shigellae were safe and immunogenic in young adults , and a Shigella sonnei conjugate conferred protection [ 1 - 3 ] . Shigellosis is primarily a disease of children ; therefore , the safety and immunogenicity of S. sonnei and Shigella flexneri 2a conjugates were studied in 4- to 7-year-old children .  Local and systemic reactions were minimal . The first injection of both conjugates elicited significant rises in geometric mean levels of serum IgG only to the homologous lipopolysaccharide ( LPS ) ( S. sonnei , 0.32 - 8.25 ELISA units [ EU ] ; S. flexneri 2a , 1.15 - 20.5 EU ; P<.0001 ) . Revaccination at 6 weeks induced a booster response to S. flexneri 2a LPS ( 20.5 - 30.5 EU , P=.003 ) . Six months later , the geometric mean levels of IgG anti-LPS for both groups were higher than the prevaccination levels ( P<.0001 ) . Similar , but lesser , rises were observed for IgM and IgA anti-LPS . The investigational Shigella conjugates were safe and immunogenic in children and merit evaluation of their efficacy Background . We conducted the first trial to assess the safety and immunogenicity of an oral , killed enterotoxigenic Escherichia coli plus cholera toxin B-subunit vaccine in children < 2 years old . Methods . Three doses of vaccine or killed E. coli K-12 control were given at 2-week intervals to 64 Egyptian infants , 6 to 18 months old , in a r and omized , double blind manner . Adverse events were monitored for 3 days after each dose . Blood was collected before immunization and 7 to 10 days after each dose to assess vaccine-specific serologic responses . Results . There was no statistically significant intergroup difference in the percentage of subjects reporting the primary safety endpoint ( diarrhea or vomiting ) after the first ( 31 % , vaccine ; 30 % , control ) or third ( 14 % , vaccine ; 18 % , control ) dose , whereas there was a trend toward greater reporting in the vaccine group after Dose 2 ( 36 % , vaccine ; 18 % , control;P = 0.052 ) . The percentage of children showing IgA seroconversion after any dose was higher in the vaccine than the control group for recombinant cholera toxin B-subunit ( 97%vs . 46 % ) , colonization factor antigen I ( 61%vs . 18 % ) and coli surface antigen 4 ( 39%vs . 4 % ) ( P < 0.001 for each comparison ) . IgG seroconversion rates in the vaccine and control groups were 97 and 21 % to recombinant cholera toxin B-subunit ( P < 0.001 ) , 64 and 29 % for colonization factor antigen I ( P < 0.01 ) , 53 and 21 % for coli surface antigen 2 ( P < 0.05 ) and 58 and 4 % for coli surface antigen 4 ( P < 0.001 ) , respectively . The third vaccine dose was followed by augmented IgG antitoxin titers . Conclusion . The oral enterotoxigenic E. coli vaccine was safe and immunogenic in this setting in Egyptian infants A field trial of oral streptomycin-dependent mutant Shigella vaccines in five hyperendemic areas of Yugoslavia in 1969 confirmed the findings of earlier studies by demonstrating the effectiveness of these vaccines against dysentery . For the first time , a high degree of protection was demonstrated in children . The vaccines induced serotype-specific immunity against Shigella flexneri 1 and 2a and S. sonnei . Postvaccinal reactions were minor and consisted of vomiting or diarrhoea , or both , in a small proportion of children within several hours of the administration of the vaccine . These reactions , seen mainly after the first dose , were dose-dependent and could be decreased by reducing the number of live organisms . Reactions to subsequent doses were much fewer . Pretreatment with sodium bicarbonate was necessary . Under the conditions of this study , the vaccines proved to be stable with no evidence of reversion of the mutant strains to the virulent parent BACKGROUND Several studies have shown that orally administered killed cholera vaccines are safe and protective in population s at risk of cholera in developing countries . However , these vaccines have not been adopted for use in developing countries because of their expense and limited efficacy in young children . We have tested an inexpensive , killed whole-cell cholera vaccine developed and produced in Vietnam . METHODS The efficacy of the vaccine was assessed in a large-scale , open field trial in people at least 1 year old residing in 22,653 households in the central coastal city of Hue . Alternate households were assigned vaccine ( 67,395 people ; two doses per person ) or no vaccine ( 67,058 people ) . Surveillance for cholera was conducted in all Ministry of Health facilities serving this population . Analysis was by intention to treat . FINDINGS During an outbreak of El Tor cholera 8 - 10 months after vaccination , 37 cases of cholera requiring inpatient care occurred among age-eligible people allocated to the vaccine group , and 92 cases among age-eligible people allocated to the no-vaccine group ( protective impact 60 % [ 95 % CI 40 - 73 ] ) . Among the 51,975 people who received the complete two-dose vaccine regimen , the protective efficacy was 66 % ( 46 - 79 ) : in this subset , the protective efficacy was similar for children aged 1 - 5 years ( 68 % ) and for older people ( 66 % ) . INTERPRETATION These findings suggest that oral killed whole-cell vaccines can confer substantial protection against El Tor cholera in young children , who are at highest risk of cholera in endemic setting s. An inexpensive , locally produced , and effective oral cholera vaccine may be within reach of the limited health-care budgets of poor countries with endemic cholera , if our findings can be replicated in a r and omised double-blind trial BACKGROUND Rotavirus gastroenteritis causes many deaths in infants in sub-Saharan Africa . Because rotavirus vaccines have proven effective in developed countries but had not been tested in developing countries , we assessed efficacy of a pentavalent rotavirus vaccine against severe disease in Ghana , Kenya , and Mali between April , 2007 , and March , 2009 . METHODS In our multicentre , double-blind , placebo-controlled trial , undertaken in rural areas of Ghana and Kenya and an urban area of Mali , we r and omly assigned infants aged 4 - 12 weeks without symptoms of gastrointestinal disorders in a 1:1 ratio to receive three oral doses of pentavalent rotavirus vaccine 2 mL or placebo at around 6 weeks , 10 weeks , and 14 weeks of age . Infants with HIV infection were not excluded . R and omisation was done by computer-generated r and omisation sequence in blocks of six . We obtained data for gastrointestinal symptoms from parents on presentation to health-care facilities and clinical data were obtained prospect ively by clinicians . The primary endpoint was severe rotavirus gastroenteritis ( Vesikari score > or=11 ) , detected by enzyme immunoassay , arising 14 days or more after the third dose of placebo or vaccine to end of study ( March 31 , 2009 ; around 21 months of age ) . Analysis was per protocol ; infants who received scheduled doses of vaccine or placebo without intervening laboratory-confirmed naturally occurring rotavirus disease earlier than 14 days after the third dose and had complete clinical and laboratory results were included in the analysis . This study is registered with Clinical Trials.gov , number NCT00362648 . FINDINGS 5468 infants were r and omly assigned to receive pentavalent rotavirus vaccine ( n=2733 ) or placebo ( n=2735 ) . 2357 infants assigned to vaccine and 2348 assigned to placebo were included in the per- protocol analysis . 79 cases of severe rotavirus gastroenteritis were reported in 2610.6 person-years in the vaccine group , compared with 129 cases in 2585.9 person-years in the placebo group , result ing in a vaccine efficacy against severe rotavirus gastroenteritis of 39.3 % ( 95 % CI 19.1 - 54.7 , p=0.0003 for efficacy > 0 % ) . Median follow-up in both groups was 527 days starting 14 days after the third dose of vaccine or placebo was given . 42 ( 1.5 % ) of 2723 infants assigned to receive vaccine and 45 ( 1.7 % ) of 2724 infants assigned to receive placebo had a serious adverse event within 14 days of any dose . The most frequent serious adverse event was gastroenteritis ( vaccine 17 [ 0.6 % ] ; placebo 17 [ 0.6 % ] ) . INTERPRETATION Pentavalent rotavirus vaccine is effective against severe rotavirus gastroenteritis in the first 2 years of life in African countries with high mortality in infants younger than 5 years . We support WHO 's recommendation for adoption of rotavirus vaccine into national exp and ed programmes on immunisation in Africa . FUNDING PATH ( GAVI Alliance grant ) and Merck This study evaluates the safety and efficacy against severe rotavirus gastroenteritis of the oral live attenuated human rotavirus vaccine RIX4414 ( Rotarix )  during the first 2 years of life in Asian infants from high-income countries . Healthy infants were enrolled to receive 2 doses of RIX4414 ( N=5,359 ) or placebo ( N=5,349 ) . From 2 weeks post-dose 2 to 2 years of age , vaccine efficacy was 96.1 % ( 95%CI:85.1 % ; 99.5 % ) against severe rotavirus gastroenteritis , 100 % ( 95%CI:80.8 % ; 100 % ) against wild-type G1P[8 ] and 93.6 % ( 95%CI:74.7 % ; 99.3 % ) against circulating non-G1 rotavirus types . No intussusception cases were reported within 31 days post-vaccination . RIX4414 shows a good safety profile and offers high protection during the first 2 years of life with potentially significant public health impact in this population BACKGROUND Despite its high worldwide morbidity and mortality , there is yet no licensed vaccine for shigellosis . We reported the safety and immunogenicity of Shigella O-specific polysaccharide-protein conjugates in adults and young children and efficacy of Shigella sonnei conjugate in young adults . METHODS A double-blinded , r and omized and vaccine-controlled Phase 3 evaluation of S. sonnei and Shigella flexneri 2a O-SP-rEPA conjugates , 25 microg , injected IM twice , 6 weeks apart , into healthy 1 - 4 years old , is reported . The children were followed for 2 years by telephone every other week and stool cultures were obtained for each episode of acute diarrhea ( > or =3 loose stools/day or a bloody/mucous stool ) . Sera were taken r and omly from 10 % of the participants for IgG anti-LPS and anti-carrier levels . RESULTS Of the 2799 enrollees , 1433 received S. sonnei and 1366 S. flexneri 2a conjugates ; 2699 ( 96.4 % ) completed the 2-year follow-up .  Local reactions occurred in approximately 5 % and approximately 4 % had temperatures > or = 38.0 degrees C lasting 1 - 2 days . There were no serious adverse events attributable to the vaccines . Of the 3295 stool cultures obtained , 125 yielded S. sonnei and 21 S. flexneri 2a . Immunogenicity and efficacy were age-related . The overall efficacy of the S. sonnei conjugate was 27.5 % ; 71.1 % ( P=0.043 ) in the 3 - 4 years old . The numbers for S. flexneri 2a were too few for meaningful analysis . Cross-protection by S. flexneri 2a for non-vaccine S. flexneri types was found , but the numbers were too few for statistical significance . There was an age-related rise of vaccine-specific IgG anti-LPS in both groups , peaking at about 10 weeks and declining thereafter , but remaining > or = 4-fold higher than in the controls 2 years after the second dose . CONCLUSIONS Shigella conjugates are safe and immunogenic in 1 - 4 years old . The S. sonnei conjugate elicited 71.1 % efficacy in the 3 - 4 years old and can be predicted to be efficacious in individuals older than 3 years of age . These results urge studies with our improved conjugates
Background Diarrhea is a leading cause of mortality in children under 5 years along with its long-term impact on growth and cognitive development .
Despite advances in the underst and ing of diarrheal disorders and management strategies , globally nearly 750,000 children die annually as a consequence of diarrhea .