The effect of azithromycin on the immunogenicity of oral poliovirus vaccine: a double-blind randomised placebo-controlled trial in seronegative Indian infants

Causes of impaired oral vaccine efficacy in developing countries

“…In a systematic review of OPV trials dating back to 1959, the presence of NPEVs at the time of vaccination (detected in stool samples in the absence of symptoms) was consistently associated with a reduction in the odds of seroconversion per dose of OPV, though it remains unclear whether this inhibitory effect varies among enterovirus species [130]. The association between the presence of NPEVs and OPV immunogenicity has since been confirmed by studies in south India [28] and Bangladesh [131] that used sensitive PCR-based methods for the detection of multiple enteric pathogens, including enteroviruses, at the time of OPV administration. In the latter study, enterovirus quantity at 10 weeks of age was also negatively correlated with the immunogenicity and efficacy of Rotarix (administered at 10 and 17 weeks) -an effect that was not observed for any other viral, bacterial or eukaryotic pathogen, or for Sabin polioviruses [131].…”

“…OPV is less immunogenic when given during warm, humid months [21,22], while Rotarix was shown to have lower immunogenicity during the cool, dry season in Zambia [23]. Oral poliovirus and rotavirus vaccines may be less immunogenic when administered in early infancy (e.g., before 6 weeks of age) compared with later infancy, although the size of this effect is small [24][25][26][27] and may be reversed at older ages [28]. The immunogenicity of live-attenuated oral cholera and typhoid vaccines given to children does not appear to be strongly related to age, although it can be affected by pre-existing immunity from natural exposure to these pathogens [29,30] inactivated oral cholera vaccines have found lower immunogenicity and efficacy among young children (<5 years of age) compared with older children [31][32][33][34].…”

“…Several studies have also highlighted the potential inhibitory effect of bacterial or eukaryotic pathogens on OPV, often in the absence of gastrointestinal symptoms [131,137,138]. However, a 3-day course of azithromycin (a broad-spectrum macrolide antibiotic) did not alter the immunogenicity of a subsequent dose of type 3 monovalent OPV among 6-11 month-old infants in India despite reducing the prevalence of bacterial pathogens (including Campylobacter, Salmonella and several pathotypes of E. coli) [28].Studies concerning the association between enteric infections and oral cholera vaccine outcome have generally focused on specific pathogens. An inhibitory association between Helicobacter pylori colonization and CVD 103-HgR response has been reported among Chilean children <5 years of age, but not in children aged 5-9 years [93].…”

“…An inhibitory association between Helicobacter pylori colonization and CVD 103-HgR response has been reported among Chilean children <5 years of age, but not in children aged 5-9 years [93]. Notably, this species is rarely documented among children <1 year of age, and is therefore unlikely to influence the immunogenicity of oral vaccines administered in early infancy [28,131]. During a placebo-controlled trial among…”

“…It is possible that the ubiquitous nature of EED in developing countries is partly responsible for this. Indeed, in several of the studies that have examined the potential association between EED and oral vaccine outcome, the majority of infants displayed elevated levels for at least one inflammatory biomarker compared with those observed in high-income countries, and it would therefore be possible to classify nearly all vaccine recipients as having some degree of EED [28,171]. In such populations, EED may contribute to oral vaccine failure despite the absence of consistent correlations between individual biomarkers and vaccine outcome.…”