Abstract
SummaryBackgroundOral vaccines underperform in low-income and middle-income countries compared with in high-income countries. Whether interventions can improve oral vaccine performance is uncertain.MethodsWe did a systematic review and meta-analysis of interventions designed to increase oral vaccine efficacy or immunogenicity. We searched Ovid-MEDLINE and Embase for trials published until Oct 23, 2017. Inclusion criteria for meta-analysis were two or more studies per intervention category and available seroconversion data. We did random-effects meta-analyses to produce summary relative risk (RR) estimates. This study is registered with PROSPERO (CRD42017060608).FindingsOf 2843 studies identified, 87 were eligible for qualitative synthesis and 66 for meta-analysis. 22 different interventions were assessed for oral poliovirus vaccine (OPV), oral rotavirus vaccine (RVV), oral cholera vaccine (OCV), and oral typhoid vaccines. There was generally high heterogeneity. Seroconversion to RVV was significantly increased by delaying the first RVV dose by 4 weeks (RR 1·37, 95% CI 1·16–1·62) and OPV seroconversion was increased with monovalent or bivalent OPV compared with trivalent OPV (RR 1·51, 95% CI 1·20–1·91). There was some evidence that separating RVV and OPV increased RVV seroconversion (RR 1·21, 95% CI 1·00–1·47) and that higher vaccine inoculum improved OCV seroconversion (RR 1·12, 95% CI 1·00–1·26). There was no evidence of effect for anthelmintics, antibiotics, probiotics, zinc, vitamin A, withholding breastfeeding, extra doses, or vaccine buffering.InterpretationMost strategies did not improve oral vaccine performance. Delaying RVV and reducing OPV valence should be considered within immunisation programmes to reduce global enteric disease. New strategies to address the gap in oral vaccine efficacy are urgently required.FundingWellcome Trust, Bill & Melinda Gates Foundation, UK Medical Research Council, and WHO Polio Research Committee.
Highlights
Despite global declines in enteric disease, approximately 650 000 children die from diarrhoea annually,[1] with rotavirus causing a third of deaths.[2]
Of the remaining two systematic reviews, both published in 2017, one examined differences in rotavirus vaccine scheduling across eight trials, concluding that seroconversion was lower among children given the vaccine earlier in infancy versus later in infancy
22 interventions were assessed (14 adjunctive inter ventions and eight vaccine design or delivery inter ventions), grouped into 17 categories: anthelmintic therapy (n=3), antibiotic therapy (n=1), probiotic supplementation (n=6), zinc supplementation (n=6), vitamin A supplementation (n=6), other micronutrient supplementation (n=3), withholding breastfeeding (n=6), extra dose or doses (n=10), extra dose given at birth (n=6), early first dose (n=1), delayed first dose (n=4), shortened interval between doses (n=5), rotavirus vaccine (RVV) given with versus without oral poliovirus vaccine (OPV) (n=7), increased vaccine inoculum (n=11), different OPV valences (n=10), inclusion of buffer (n=11), and miscellaneous (n=4, appendix p 4)
Summary
Despite global declines in enteric disease, approximately 650 000 children die from diarrhoea annually,[1] with rotavirus causing a third of deaths.[2]. Potential explanations include concurrent enteric infections,[9,10] microbiota composition,[11] environmental enteric dysfunction,[12] interference from maternal antibodies,[13,14] histoblood group antigens,[15] and micronutrient deficiencies.[16,17] The relative contributions of these factors can vary depending on oral vaccine target, recipient age, and setting
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
