A Two-Center Randomized Trial of an Additional Early Dose of Measles Vaccine: Effects on Mortality and Measles Antibody Levels

Ane B Fisker, Eric Nebie, Anja Schoeps, Cesario Martins, Amabelia Rodrigues, Alphonse Zakane, Moubassira Kagone, Stine Byberg, Sanne M Thysen, Justin Tiendrebeogo, Boubacar Coulibaly, Osman Sankoh, Heiko Becher, Hilton C Whittle, Fiona R M van der Klis, Christine S Benn, Ali Sie, Olaf Müller, Peter Aaby

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Background In addition to protecting against measles, measles vaccine (MV) may have beneficial nonspecific effects. We tested the effect of an additional early MV on mortality and measles antibody levels. Methods Children aged 4-7 months at rural health and demographic surveillance sites in Burkina Faso and Guinea-Bissau were randomized 1:1 to an extra early standard dose of MV (Edmonston-Zagreb strain) or no extra MV 4 weeks after the third diphtheria-tetanus-pertussis-hepatitis B-Haemophilus influenzae type b vaccine. All children received routine MV at 9 months. We assessed mortality through home visits and compared mortality from enrollment to age 3 years using Cox proportional hazards models, censoring for subsequent nontrial MV. Subgroups of participants had blood sampled to assess measles antibody levels. Results Among 8309 children enrolled from 18 July 2012 to 3 December 2015, we registered 145 deaths (mortality rate: 16/1000 person-years). The mortality was lower than anticipated and did not differ by randomization group (hazard ratio, 1.05; 95% confidence interval, 0.75-1.46). At enrollment, 4% (16/447) of children in Burkina Faso and 21% (90/422) in Guinea-Bissau had protective measles antibody levels. By age 9 months, no measles-unvaccinated/-unexposed child had protective levels, while 92% (306/333) of early MV recipients had protective levels. At final follow-up, 98% (186/189) in the early MV group and 97% (196/202) in the control group had protective levels. Conclusions Early MV did not reduce all-cause mortality. Most children were susceptible to measles infection at age 4-7 months and responded with high antibody levels to early MV. Clinical Trials Registration NCT01644721.

OriginalsprogEngelsk
TidsskriftClinical Infectious Diseases
Vol/bind66
Udgave nummer10
Sider (fra-til)1573–1580
ISSN1058-4838
DOI
StatusUdgivet - 2. maj 2018

Fingeraftryk

Measles
Guinea-Bissau
Haemophilus Vaccines
Rural Health
Haemophilus influenzae type b
House Calls
Diphtheria
Whooping Cough
Random Allocation
Hepatitis B
Proportional Hazards Models
Clinical Trials
Confidence Intervals
Control Groups

Citer dette

Fisker, Ane B ; Nebie, Eric ; Schoeps, Anja ; Martins, Cesario ; Rodrigues, Amabelia ; Zakane, Alphonse ; Kagone, Moubassira ; Byberg, Stine ; Thysen, Sanne M ; Tiendrebeogo, Justin ; Coulibaly, Boubacar ; Sankoh, Osman ; Becher, Heiko ; Whittle, Hilton C ; van der Klis, Fiona R M ; Benn, Christine S ; Sie, Ali ; Müller, Olaf ; Aaby, Peter. / A Two-Center Randomized Trial of an Additional Early Dose of Measles Vaccine : Effects on Mortality and Measles Antibody Levels. I: Clinical Infectious Diseases. 2018 ; Bind 66, Nr. 10. s. 1573–1580.
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abstract = "Background In addition to protecting against measles, measles vaccine (MV) may have beneficial nonspecific effects. We tested the effect of an additional early MV on mortality and measles antibody levels. Methods Children aged 4-7 months at rural health and demographic surveillance sites in Burkina Faso and Guinea-Bissau were randomized 1:1 to an extra early standard dose of MV (Edmonston-Zagreb strain) or no extra MV 4 weeks after the third diphtheria-tetanus-pertussis-hepatitis B-Haemophilus influenzae type b vaccine. All children received routine MV at 9 months. We assessed mortality through home visits and compared mortality from enrollment to age 3 years using Cox proportional hazards models, censoring for subsequent nontrial MV. Subgroups of participants had blood sampled to assess measles antibody levels. Results Among 8309 children enrolled from 18 July 2012 to 3 December 2015, we registered 145 deaths (mortality rate: 16/1000 person-years). The mortality was lower than anticipated and did not differ by randomization group (hazard ratio, 1.05; 95{\%} confidence interval, 0.75-1.46). At enrollment, 4{\%} (16/447) of children in Burkina Faso and 21{\%} (90/422) in Guinea-Bissau had protective measles antibody levels. By age 9 months, no measles-unvaccinated/-unexposed child had protective levels, while 92{\%} (306/333) of early MV recipients had protective levels. At final follow-up, 98{\%} (186/189) in the early MV group and 97{\%} (196/202) in the control group had protective levels. Conclusions Early MV did not reduce all-cause mortality. Most children were susceptible to measles infection at age 4-7 months and responded with high antibody levels to early MV. Clinical Trials Registration NCT01644721.",
keywords = "child mortality, heterologous (nonspecific) effects of vaccines, measles antibody levels, measles vaccination",
author = "Fisker, {Ane B} and Eric Nebie and Anja Schoeps and Cesario Martins and Amabelia Rodrigues and Alphonse Zakane and Moubassira Kagone and Stine Byberg and Thysen, {Sanne M} and Justin Tiendrebeogo and Boubacar Coulibaly and Osman Sankoh and Heiko Becher and Whittle, {Hilton C} and {van der Klis}, {Fiona R M} and Benn, {Christine S} and Ali Sie and Olaf M{\"u}ller and Peter Aaby",
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Fisker, AB, Nebie, E, Schoeps, A, Martins, C, Rodrigues, A, Zakane, A, Kagone, M, Byberg, S, Thysen, SM, Tiendrebeogo, J, Coulibaly, B, Sankoh, O, Becher, H, Whittle, HC, van der Klis, FRM, Benn, CS, Sie, A, Müller, O & Aaby, P 2018, 'A Two-Center Randomized Trial of an Additional Early Dose of Measles Vaccine: Effects on Mortality and Measles Antibody Levels', Clinical Infectious Diseases, bind 66, nr. 10, s. 1573–1580. https://doi.org/10.1093/cid/cix1033

A Two-Center Randomized Trial of an Additional Early Dose of Measles Vaccine : Effects on Mortality and Measles Antibody Levels. / Fisker, Ane B; Nebie, Eric; Schoeps, Anja; Martins, Cesario; Rodrigues, Amabelia; Zakane, Alphonse; Kagone, Moubassira; Byberg, Stine; Thysen, Sanne M; Tiendrebeogo, Justin; Coulibaly, Boubacar; Sankoh, Osman; Becher, Heiko; Whittle, Hilton C; van der Klis, Fiona R M; Benn, Christine S; Sie, Ali; Müller, Olaf; Aaby, Peter.

I: Clinical Infectious Diseases, Bind 66, Nr. 10, 02.05.2018, s. 1573–1580.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - A Two-Center Randomized Trial of an Additional Early Dose of Measles Vaccine

T2 - Effects on Mortality and Measles Antibody Levels

AU - Fisker, Ane B

AU - Nebie, Eric

AU - Schoeps, Anja

AU - Martins, Cesario

AU - Rodrigues, Amabelia

AU - Zakane, Alphonse

AU - Kagone, Moubassira

AU - Byberg, Stine

AU - Thysen, Sanne M

AU - Tiendrebeogo, Justin

AU - Coulibaly, Boubacar

AU - Sankoh, Osman

AU - Becher, Heiko

AU - Whittle, Hilton C

AU - van der Klis, Fiona R M

AU - Benn, Christine S

AU - Sie, Ali

AU - Müller, Olaf

AU - Aaby, Peter

PY - 2018/5/2

Y1 - 2018/5/2

N2 - Background In addition to protecting against measles, measles vaccine (MV) may have beneficial nonspecific effects. We tested the effect of an additional early MV on mortality and measles antibody levels. Methods Children aged 4-7 months at rural health and demographic surveillance sites in Burkina Faso and Guinea-Bissau were randomized 1:1 to an extra early standard dose of MV (Edmonston-Zagreb strain) or no extra MV 4 weeks after the third diphtheria-tetanus-pertussis-hepatitis B-Haemophilus influenzae type b vaccine. All children received routine MV at 9 months. We assessed mortality through home visits and compared mortality from enrollment to age 3 years using Cox proportional hazards models, censoring for subsequent nontrial MV. Subgroups of participants had blood sampled to assess measles antibody levels. Results Among 8309 children enrolled from 18 July 2012 to 3 December 2015, we registered 145 deaths (mortality rate: 16/1000 person-years). The mortality was lower than anticipated and did not differ by randomization group (hazard ratio, 1.05; 95% confidence interval, 0.75-1.46). At enrollment, 4% (16/447) of children in Burkina Faso and 21% (90/422) in Guinea-Bissau had protective measles antibody levels. By age 9 months, no measles-unvaccinated/-unexposed child had protective levels, while 92% (306/333) of early MV recipients had protective levels. At final follow-up, 98% (186/189) in the early MV group and 97% (196/202) in the control group had protective levels. Conclusions Early MV did not reduce all-cause mortality. Most children were susceptible to measles infection at age 4-7 months and responded with high antibody levels to early MV. Clinical Trials Registration NCT01644721.

AB - Background In addition to protecting against measles, measles vaccine (MV) may have beneficial nonspecific effects. We tested the effect of an additional early MV on mortality and measles antibody levels. Methods Children aged 4-7 months at rural health and demographic surveillance sites in Burkina Faso and Guinea-Bissau were randomized 1:1 to an extra early standard dose of MV (Edmonston-Zagreb strain) or no extra MV 4 weeks after the third diphtheria-tetanus-pertussis-hepatitis B-Haemophilus influenzae type b vaccine. All children received routine MV at 9 months. We assessed mortality through home visits and compared mortality from enrollment to age 3 years using Cox proportional hazards models, censoring for subsequent nontrial MV. Subgroups of participants had blood sampled to assess measles antibody levels. Results Among 8309 children enrolled from 18 July 2012 to 3 December 2015, we registered 145 deaths (mortality rate: 16/1000 person-years). The mortality was lower than anticipated and did not differ by randomization group (hazard ratio, 1.05; 95% confidence interval, 0.75-1.46). At enrollment, 4% (16/447) of children in Burkina Faso and 21% (90/422) in Guinea-Bissau had protective measles antibody levels. By age 9 months, no measles-unvaccinated/-unexposed child had protective levels, while 92% (306/333) of early MV recipients had protective levels. At final follow-up, 98% (186/189) in the early MV group and 97% (196/202) in the control group had protective levels. Conclusions Early MV did not reduce all-cause mortality. Most children were susceptible to measles infection at age 4-7 months and responded with high antibody levels to early MV. Clinical Trials Registration NCT01644721.

KW - child mortality

KW - heterologous (nonspecific) effects of vaccines

KW - measles antibody levels

KW - measles vaccination

U2 - 10.1093/cid/cix1033

DO - 10.1093/cid/cix1033

M3 - Journal article

C2 - 29177407

VL - 66

SP - 1573

EP - 1580

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

SN - 1058-4838

IS - 10

ER -