Does oral polio vaccine have non-specific effects on all-cause mortality? Natural experiments within a randomised controlled trial of early measles vaccine

Aaby, Péter; Andersen, Andreas; Martins, Cesário; Fisker, Ane Bærent; Rodrigues, Amabélia; Whittle, Hilton; Benn, Christine Stabell

doi:10.1136/bmjopen-2016-013335

Cited by 37 publications

(44 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This could reduce all-cause child mortality substantially in low-income countries with high mortality. We have used this strategy successfully in Guinea-Bissau when two doses of MV at 4.5 and 9 months were associated with a 30% reduction in mortality between 4.5 and 36 months of age (3,30). In two subsequent RCTs of two-dose MV in Guinea-Bissau and Burkina Faso we found no beneficial effect of early MV (31).…”

Section: Interpretation and Implicationsmentioning

confidence: 93%

“…During these latter RCTs many mothers were vaccinated and levels of maternal measles antibody were low and consequently fewer children were vaccinated in the presence of maternal antibody. In addition there were numerous campaigns with oral polio vaccine (OPV) and this may have reduced or removed the benefit from early MV (30,31); we have previously shown that neonatal vitamin A supplementation (NVAS) may also remove the benefit of early MV (3). The marked benefit of early MV may therefore be affected by other interventions.…”

Section: Interpretation and Implicationsmentioning

confidence: 99%

See 1 more Smart Citation

Measles Vaccination in Presence of Measles Antibody May Enhance Child Survival

et al. 2020

Self Cite

View full text Add to dashboard Cite

Background: In trials of early two-dose measles vaccination (MV), with the first dose being given before 9 months of age, vaccination in the presence of maternal antibody reduced mortality 2-to 3-fold compared with MV in the presence of no measles antibody. We tested this finding in two historical studies in which the children had received one dose of MV.Methods: We used data from a surveillance study of seroconversion after standard-titer MV (Schwarz strain) (Study 1) and a trial of early medium-titer MV (Edmonston-Zagreb strain) in which a pre-vaccination blood sample had been collected (Study 2). Both studies had control children, who were enrolled under similar conditions, but did not receive effective MV. Study 1 was a natural experiment where all children measles vaccinated during 1 month did not seroconvert and had therefore received an ineffective vaccine. In Study 2, the controls were randomized to an inactivated polio vaccine (IPV). We compared mortality for children with undetectable levels of measles antibody (<31.25 mIU) at baseline with children with detectable levels (≥31.25 mIU). Results:In both studies, children who were measles vaccinated in the presence of measles antibody had lower mortality compared with children who were measles vaccinated in presence of no measles antibody, the combined mortality rate ratio (MRR) being 0.51 (0.27-0.96). In the control groups, a detectable level of measles antibody vs. an undetectable level was not associated with lower mortality, the MRR being 1.40 (0.31-6.38). Conclusion:The results supported previous findings: measles vaccination in the presence of measles antibody had beneficial effects on child survival. Since maternal antibody levels are declining, it may be time to consider giving MV earlier and/or to provide MV to adolescent girls to boost antibody levels.

show abstract

Section: Interpretation and Implicationsmentioning

confidence: 93%

Section: Interpretation and Implicationsmentioning

confidence: 99%

Measles Vaccination in Presence of Measles Antibody May Enhance Child Survival

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…Rather than the "certainty" of the beneficial NSEs of MV, focus should also be on what other factors might affect the NSEs of MV. For example, we have found that routine OPV, OPV-campaigns and vitamin Acampaigns may modulate the NSEs of MV [22,25,48].…”

Section: The Way Forwardmentioning

confidence: 97%

“…Second, several studies have shown OPV-campaigns to be associated with a marked decline in the general mortality rate [45][46][47]. Third, OPV campaigns have modified estimated mortality outcomes in studies of other vaccines [45,48].…”

Section: Example: Oral Polio Vaccinementioning

confidence: 99%

See 1 more Smart Citation

How to evaluate potential non-specific effects of vaccines: the quest for randomized trials or time for triangulation?

Benn

Fisker

Rieckmann

et al. 2018

Expert Review of Vaccines

Self Cite

View full text Add to dashboard Cite

Emerging evidence suggests that vaccines, in addition to their disease-specific effects, have important non-specific effects (NSEs), which contribute to their overall effect on mortality and morbidity. Immunological studies have shown that NSEs are biologically plausible. Many advocate that randomized controlled trials (RCTs) with overall mortality or morbidity as the outcome are the only way forward to confirm or refute NSEs. Areas covered: We discuss the limitations of using RCTs only as a tool to evaluate NSEs of vaccines. Such RCTs can be ethically problematic, they are time consuming and expensive. Furthermore, they only assess the NSEs in a given context, but it is inherent in the concept of NSEs that the NSEs of a given vaccine are modified by other immunomodulatory conditions. As an alternative, we propose that triangulation of RCTs and observational studies, merging multiple lines of evidence with different underlying bias structures, can build a strong argument for causality. We examine two examples related to measles vaccine and oral polio vaccine. Expert commentary: Using RCTs alone to evaluate NSEs of vaccines severely limits the possibilities for studying NSEs. Results from both RCTs and non-RCT studies should be triangulated to strengthen causal interpretation.

show abstract

Implications of Non-Specific Effects for Testing, Approving, and Regulating Vaccines

et al. 2023

Self Cite

View full text Add to dashboard Cite

The current framework for testing and regulating vaccines was established before the realization that vaccines, in addition to their effect against the vaccine-specific disease, may also have “non-specific effects” affecting the risk of unrelated diseases. Accumulating evidence from epidemiological studies shows that vaccines in some situations can affect all-cause mortality and morbidity in ways that are not explained by the prevention of the vaccine-targeted disease. Live attenuated vaccines have sometimes been associated with decreases in mortality and morbidity that are greater than anticipated. In contrast, some non-live vaccines have in certain contexts been associated with increases in all-cause mortality and morbidity. The non-specific effects are often greater for female than male individuals. Immunological studies have provided several mechanisms that explain how vaccines might modulate the immune response to unrelated pathogens, such as through trained innate immunity, emergency granulopoiesis, and heterologous T-cell immunity. These insights suggest that the framework for the testing, approving, and regulating vaccines needs to be updated to accommodate non-specific effects. Currently, non-specific effects are not routinely captured in phase I–III clinical trials or in the post-licensure safety surveillance. For instance, an infection with Streptococcus pneumoniae occurring months after a diphtheria-tetanus-pertussis vaccination would not be considered an effect of the vaccination, although evidence indicates it might well be for female individuals. Here, as a starting point for discussion, we propose a new framework that considers the non-specific effects of vaccines in both phase III trials and post-licensure.

show abstract

Does oral polio vaccine have non-specific effects on all-cause mortality? Natural experiments within a randomised controlled trial of early measles vaccine

Cited by 37 publications

References 33 publications

Measles Vaccination in Presence of Measles Antibody May Enhance Child Survival

Measles Vaccination in Presence of Measles Antibody May Enhance Child Survival

How to evaluate potential non-specific effects of vaccines: the quest for randomized trials or time for triangulation?

Implications of Non-Specific Effects for Testing, Approving, and Regulating Vaccines

Contact Info

Product

Resources

About