No effect of an additional early dose of measles vaccine on hospitalization or mortality in children: A randomized controlled trial

TY - JOUR

T1 - No effect of an additional early dose of measles vaccine on hospitalization or mortality in children: A randomized controlled trial

AU - Schoeps, Anja

AU - Nebié, Eric

AU - Fisker, Ane Baerent

AU - Sié, Ali

AU - Zakane, Alphonse

AU - Müller, Olaf

AU - Aaby, Peter

AU - Becher, Heiko

N1 - Copyright © 2018 Elsevier Ltd. All rights reserved.

PY - 2018/4/5

Y1 - 2018/4/5

N2 - BACKGROUND: Non-specific effects (NSEs) of vaccines have increasingly gained attention in recent years. Recent studies suggest that live vaccines, such as measles vaccine (MV), have beneficial effects on health, while inactivated vaccines, such as the diphtheria-tetanus-pertussis (DTP) vaccine, may have harmful effects. If this is the case, it should improve child health to move MV closer to the last vaccination with DTP. The objective of this study was to investigate the NSEs of an additional early dose of MV on hospitalization or mortality.METHODS: Children were randomized to receive either the standard MV at 9 months (control) or an additional early dose of MV 4 weeks after the third dose of DTP-containing Pentavalent vaccine and the standard MV at 9 months (intervention). In this analysis of a secondary outcome in the trial, we investigated the effect of the intervention on a composite endpoint of over-night hospitalization with or without recovery, or death without previous hospitalization, in children between 4.5 and 36 months of age in the Nouna HDSS in Burkina Faso. We used Cox proportional hazards regression with repeated events and time since study enrolment as underlying time-scale.RESULTS: Among 2258 children in the intervention and 2238 children in the control group we observed a total of 464 episodes of hospitalization or mortality. There was no difference between intervention and control group (HR = 1.00, 95% Confidence Interval (CI) 0.83-1.20). Results from the per-protocol and intention-to-treat analysis were similar. Although no significant, results suggest a possible beneficial effect of early MV in children that had not been exposed to an OPV campaign after enrolment (HR = 0.83, 95% CI 0.55-1.29).CONCLUSIONS: We did not detect any effect of early MV on subsequent hospitalization or mortality. However, possible effects of early MV could have been obscured by NSEs of the frequent OPV campaigns. Registration: The trial was registered at ClinicalTrials.gov, NCT01644721.

AB - BACKGROUND: Non-specific effects (NSEs) of vaccines have increasingly gained attention in recent years. Recent studies suggest that live vaccines, such as measles vaccine (MV), have beneficial effects on health, while inactivated vaccines, such as the diphtheria-tetanus-pertussis (DTP) vaccine, may have harmful effects. If this is the case, it should improve child health to move MV closer to the last vaccination with DTP. The objective of this study was to investigate the NSEs of an additional early dose of MV on hospitalization or mortality.METHODS: Children were randomized to receive either the standard MV at 9 months (control) or an additional early dose of MV 4 weeks after the third dose of DTP-containing Pentavalent vaccine and the standard MV at 9 months (intervention). In this analysis of a secondary outcome in the trial, we investigated the effect of the intervention on a composite endpoint of over-night hospitalization with or without recovery, or death without previous hospitalization, in children between 4.5 and 36 months of age in the Nouna HDSS in Burkina Faso. We used Cox proportional hazards regression with repeated events and time since study enrolment as underlying time-scale.RESULTS: Among 2258 children in the intervention and 2238 children in the control group we observed a total of 464 episodes of hospitalization or mortality. There was no difference between intervention and control group (HR = 1.00, 95% Confidence Interval (CI) 0.83-1.20). Results from the per-protocol and intention-to-treat analysis were similar. Although no significant, results suggest a possible beneficial effect of early MV in children that had not been exposed to an OPV campaign after enrolment (HR = 0.83, 95% CI 0.55-1.29).CONCLUSIONS: We did not detect any effect of early MV on subsequent hospitalization or mortality. However, possible effects of early MV could have been obscured by NSEs of the frequent OPV campaigns. Registration: The trial was registered at ClinicalTrials.gov, NCT01644721.

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.vaccine.2018.02.104

DO - 10.1016/j.vaccine.2018.02.104

M3 - SCORING: Journal article

C2 - 29523450

VL - 36

SP - 1965

EP - 1971

JO - VACCINE

JF - VACCINE

SN - 0264-410X

IS - 15

ER -