Effectiveness of a live oral human rotavirus vaccine after programmatic introduction in Bangladesh: A cluster-randomized trial

K. Zaman, David A. Sack, Kathleen M. Neuzil, Mohammad Yunus, Lawrence H. Moulton, Jonathan D. Sugimoto, Jessica A. Fleming, Ilias Hossain, Shams El Arifeen, Tasnim Azim, Mustafizur Rahman, Kristen D.C. Lewis, Andrea J. Feller, Firdausi Qadri, M. Elizabeth Halloran, Alejandro Cravioto, John C. Victor

Research output: Contribution to journalArticle

Abstract

Background: Rotavirus vaccines are now globally recommended by the World Health Organization (WHO), but in early 2009 WHO’s Strategic Advisory Group of Experts on Immunization reviewed available data and concluded that there was no evidence for the efficacy or effectiveness of a two-dose schedule of the human rotavirus vaccine (HRV; Rotarix) given early at 6 and 10 wk of age. Additionally, the effectiveness of programmatic rotavirus vaccination, including possible indirect effects, has not been assessed in low-resource populations in Asia. Methods and findings: In Bangladesh, we cluster-randomized (1:1) 142 villages of the Matlab Health and Demographic Surveillance System to include two doses of HRV with the standard infant vaccines at 6 and 10 wk of age or to provide standard infant vaccines without HRV. The study was initiated November 1, 2008, and surveillance was conducted concurrently at Matlab Diarrhoea Hospital and two community treatment centers to identify children less than 2 y of age presenting with acute rotavirus diarrhea (ARD) through March 31, 2011. Laboratory confirmation was made by enzyme immunoassay detection of rotavirus antigen in stool specimens. Overall effectiveness of the HRV vaccination program (primary objective) was measured by comparing the incidence rate of ARD among all children age-eligible for vaccination in villages where HRV was introduced to that among such children in villages where HRV was not introduced. Total effectiveness among vaccinees and indirect effectiveness were also evaluated. In all, 6,527 infants were age-eligible for vaccination in 71 HRV villages, and 5,791 in 71 non-HRV villages. In HRV villages, 4,808 (73.7%) infants received at least one dose of HRV. The incidence rate of ARD was 4.10 cases per 100 person-years in non-HRV villages compared to 2.8 per 100 person-years in HRV villages, indicating an overall effectiveness of 29.0% (95% CI, 11.3% to 43.1%). The total effectiveness of HRV against ARD among vaccinees was 41.4% (95% CI, 23.2% to 55.2%). The point estimate for total effectiveness was higher against ARD during the first year of life than during the second (45.2% versus 28.9%), but estimates for the second year of life lacked precision and did not reach statistical significance. Indirect effects were not detected. To check for bias in presentation to treatment facilities, we evaluated the effectiveness of HRV against acute diarrhea associated with enterotoxigenic Escherichia coli; it was 4.0% (95% CI, −46.5% to 37.1%), indicating that bias likely was not introduced. Thirteen serious adverse events were identified among recipients of HRV, but none were considered related to receipt of study vaccine. The main limitation of this study is that it was an open-label study with an observed-only control group (no placebo). Conclusions: The two-dose HRV rotavirus vaccination program significantly reduced medically attended ARD in this low-resource population in Asia. Protection among vaccinees was similar to that in other low-resource settings. In low-resource populations with high rotavirus incidence, large-scale vaccination across a wide population may be required to obtain the full benefit of rotavirus vaccination, including indirect effects. Trial registration: ClinicalTrials.gov NCT00737503.

Original languageEnglish (US)
Article numbere1002282
JournalPLoS Medicine
Volume14
Issue number4
DOIs
StatePublished - 2017

Fingerprint

Rotavirus Vaccines
Bangladesh
Rotavirus
Jejunoileal Bypass
Diarrhea
Acromegaly
Vaccination
Frangula
Acromion
Immunization
Blood Flow Velocity
Labels
Vaccines
Incidence
Enterotoxigenic Escherichia coli
Immunoenzyme Techniques
Appointments and Schedules
Placebos
Demography
Antigens

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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Effectiveness of a live oral human rotavirus vaccine after programmatic introduction in Bangladesh : A cluster-randomized trial. / Zaman, K.; Sack, David A.; Neuzil, Kathleen M.; Yunus, Mohammad; Moulton, Lawrence H.; Sugimoto, Jonathan D.; Fleming, Jessica A.; Hossain, Ilias; Arifeen, Shams El; Azim, Tasnim; Rahman, Mustafizur; Lewis, Kristen D.C.; Feller, Andrea J.; Qadri, Firdausi; Halloran, M. Elizabeth; Cravioto, Alejandro; Victor, John C.

In: PLoS Medicine, Vol. 14, No. 4, e1002282, 2017.

Research output: Contribution to journalArticle

Zaman, K, Sack, DA, Neuzil, KM, Yunus, M, Moulton, LH, Sugimoto, JD, Fleming, JA, Hossain, I, Arifeen, SE, Azim, T, Rahman, M, Lewis, KDC, Feller, AJ, Qadri, F, Halloran, ME, Cravioto, A & Victor, JC 2017, 'Effectiveness of a live oral human rotavirus vaccine after programmatic introduction in Bangladesh: A cluster-randomized trial' PLoS Medicine, vol 14, no. 4, e1002282. DOI: 10.1371/journal.pmed.1002282

Zaman, K.; Sack, David A.; Neuzil, Kathleen M.; Yunus, Mohammad; Moulton, Lawrence H.; Sugimoto, Jonathan D.; Fleming, Jessica A.; Hossain, Ilias; Arifeen, Shams El; Azim, Tasnim; Rahman, Mustafizur; Lewis, Kristen D.C.; Feller, Andrea J.; Qadri, Firdausi; Halloran, M. Elizabeth; Cravioto, Alejandro; Victor, John C. / Effectiveness of a live oral human rotavirus vaccine after programmatic introduction in Bangladesh : A cluster-randomized trial.

In: PLoS Medicine, Vol. 14, No. 4, e1002282, 2017.

Research output: Contribution to journalArticle

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abstract = "Background: Rotavirus vaccines are now globally recommended by the World Health Organization (WHO), but in early 2009 WHO’s Strategic Advisory Group of Experts on Immunization reviewed available data and concluded that there was no evidence for the efficacy or effectiveness of a two-dose schedule of the human rotavirus vaccine (HRV; Rotarix) given early at 6 and 10 wk of age. Additionally, the effectiveness of programmatic rotavirus vaccination, including possible indirect effects, has not been assessed in low-resource populations in Asia. Methods and findings: In Bangladesh, we cluster-randomized (1:1) 142 villages of the Matlab Health and Demographic Surveillance System to include two doses of HRV with the standard infant vaccines at 6 and 10 wk of age or to provide standard infant vaccines without HRV. The study was initiated November 1, 2008, and surveillance was conducted concurrently at Matlab Diarrhoea Hospital and two community treatment centers to identify children less than 2 y of age presenting with acute rotavirus diarrhea (ARD) through March 31, 2011. Laboratory confirmation was made by enzyme immunoassay detection of rotavirus antigen in stool specimens. Overall effectiveness of the HRV vaccination program (primary objective) was measured by comparing the incidence rate of ARD among all children age-eligible for vaccination in villages where HRV was introduced to that among such children in villages where HRV was not introduced. Total effectiveness among vaccinees and indirect effectiveness were also evaluated. In all, 6,527 infants were age-eligible for vaccination in 71 HRV villages, and 5,791 in 71 non-HRV villages. In HRV villages, 4,808 (73.7%) infants received at least one dose of HRV. The incidence rate of ARD was 4.10 cases per 100 person-years in non-HRV villages compared to 2.8 per 100 person-years in HRV villages, indicating an overall effectiveness of 29.0% (95% CI, 11.3% to 43.1%). The total effectiveness of HRV against ARD among vaccinees was 41.4% (95% CI, 23.2% to 55.2%). The point estimate for total effectiveness was higher against ARD during the first year of life than during the second (45.2% versus 28.9%), but estimates for the second year of life lacked precision and did not reach statistical significance. Indirect effects were not detected. To check for bias in presentation to treatment facilities, we evaluated the effectiveness of HRV against acute diarrhea associated with enterotoxigenic Escherichia coli; it was 4.0% (95% CI, −46.5% to 37.1%), indicating that bias likely was not introduced. Thirteen serious adverse events were identified among recipients of HRV, but none were considered related to receipt of study vaccine. The main limitation of this study is that it was an open-label study with an observed-only control group (no placebo). Conclusions: The two-dose HRV rotavirus vaccination program significantly reduced medically attended ARD in this low-resource population in Asia. Protection among vaccinees was similar to that in other low-resource settings. In low-resource populations with high rotavirus incidence, large-scale vaccination across a wide population may be required to obtain the full benefit of rotavirus vaccination, including indirect effects. Trial registration: ClinicalTrials.gov NCT00737503.",
author = "K. Zaman and Sack, {David A.} and Neuzil, {Kathleen M.} and Mohammad Yunus and Moulton, {Lawrence H.} and Sugimoto, {Jonathan D.} and Fleming, {Jessica A.} and Ilias Hossain and Arifeen, {Shams El} and Tasnim Azim and Mustafizur Rahman and Lewis, {Kristen D.C.} and Feller, {Andrea J.} and Firdausi Qadri and Halloran, {M. Elizabeth} and Alejandro Cravioto and Victor, {John C.}",
year = "2017",
doi = "10.1371/journal.pmed.1002282",
volume = "14",
journal = "PLoS Medicine",
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TY - JOUR

T1 - Effectiveness of a live oral human rotavirus vaccine after programmatic introduction in Bangladesh

T2 - PLoS Medicine

AU - Zaman,K.

AU - Sack,David A.

AU - Neuzil,Kathleen M.

AU - Yunus,Mohammad

AU - Moulton,Lawrence H.

AU - Sugimoto,Jonathan D.

AU - Fleming,Jessica A.

AU - Hossain,Ilias

AU - Arifeen,Shams El

AU - Azim,Tasnim

AU - Rahman,Mustafizur

AU - Lewis,Kristen D.C.

AU - Feller,Andrea J.

AU - Qadri,Firdausi

AU - Halloran,M. Elizabeth

AU - Cravioto,Alejandro

AU - Victor,John C.

PY - 2017

Y1 - 2017

N2 - Background: Rotavirus vaccines are now globally recommended by the World Health Organization (WHO), but in early 2009 WHO’s Strategic Advisory Group of Experts on Immunization reviewed available data and concluded that there was no evidence for the efficacy or effectiveness of a two-dose schedule of the human rotavirus vaccine (HRV; Rotarix) given early at 6 and 10 wk of age. Additionally, the effectiveness of programmatic rotavirus vaccination, including possible indirect effects, has not been assessed in low-resource populations in Asia. Methods and findings: In Bangladesh, we cluster-randomized (1:1) 142 villages of the Matlab Health and Demographic Surveillance System to include two doses of HRV with the standard infant vaccines at 6 and 10 wk of age or to provide standard infant vaccines without HRV. The study was initiated November 1, 2008, and surveillance was conducted concurrently at Matlab Diarrhoea Hospital and two community treatment centers to identify children less than 2 y of age presenting with acute rotavirus diarrhea (ARD) through March 31, 2011. Laboratory confirmation was made by enzyme immunoassay detection of rotavirus antigen in stool specimens. Overall effectiveness of the HRV vaccination program (primary objective) was measured by comparing the incidence rate of ARD among all children age-eligible for vaccination in villages where HRV was introduced to that among such children in villages where HRV was not introduced. Total effectiveness among vaccinees and indirect effectiveness were also evaluated. In all, 6,527 infants were age-eligible for vaccination in 71 HRV villages, and 5,791 in 71 non-HRV villages. In HRV villages, 4,808 (73.7%) infants received at least one dose of HRV. The incidence rate of ARD was 4.10 cases per 100 person-years in non-HRV villages compared to 2.8 per 100 person-years in HRV villages, indicating an overall effectiveness of 29.0% (95% CI, 11.3% to 43.1%). The total effectiveness of HRV against ARD among vaccinees was 41.4% (95% CI, 23.2% to 55.2%). The point estimate for total effectiveness was higher against ARD during the first year of life than during the second (45.2% versus 28.9%), but estimates for the second year of life lacked precision and did not reach statistical significance. Indirect effects were not detected. To check for bias in presentation to treatment facilities, we evaluated the effectiveness of HRV against acute diarrhea associated with enterotoxigenic Escherichia coli; it was 4.0% (95% CI, −46.5% to 37.1%), indicating that bias likely was not introduced. Thirteen serious adverse events were identified among recipients of HRV, but none were considered related to receipt of study vaccine. The main limitation of this study is that it was an open-label study with an observed-only control group (no placebo). Conclusions: The two-dose HRV rotavirus vaccination program significantly reduced medically attended ARD in this low-resource population in Asia. Protection among vaccinees was similar to that in other low-resource settings. In low-resource populations with high rotavirus incidence, large-scale vaccination across a wide population may be required to obtain the full benefit of rotavirus vaccination, including indirect effects. Trial registration: ClinicalTrials.gov NCT00737503.

AB - Background: Rotavirus vaccines are now globally recommended by the World Health Organization (WHO), but in early 2009 WHO’s Strategic Advisory Group of Experts on Immunization reviewed available data and concluded that there was no evidence for the efficacy or effectiveness of a two-dose schedule of the human rotavirus vaccine (HRV; Rotarix) given early at 6 and 10 wk of age. Additionally, the effectiveness of programmatic rotavirus vaccination, including possible indirect effects, has not been assessed in low-resource populations in Asia. Methods and findings: In Bangladesh, we cluster-randomized (1:1) 142 villages of the Matlab Health and Demographic Surveillance System to include two doses of HRV with the standard infant vaccines at 6 and 10 wk of age or to provide standard infant vaccines without HRV. The study was initiated November 1, 2008, and surveillance was conducted concurrently at Matlab Diarrhoea Hospital and two community treatment centers to identify children less than 2 y of age presenting with acute rotavirus diarrhea (ARD) through March 31, 2011. Laboratory confirmation was made by enzyme immunoassay detection of rotavirus antigen in stool specimens. Overall effectiveness of the HRV vaccination program (primary objective) was measured by comparing the incidence rate of ARD among all children age-eligible for vaccination in villages where HRV was introduced to that among such children in villages where HRV was not introduced. Total effectiveness among vaccinees and indirect effectiveness were also evaluated. In all, 6,527 infants were age-eligible for vaccination in 71 HRV villages, and 5,791 in 71 non-HRV villages. In HRV villages, 4,808 (73.7%) infants received at least one dose of HRV. The incidence rate of ARD was 4.10 cases per 100 person-years in non-HRV villages compared to 2.8 per 100 person-years in HRV villages, indicating an overall effectiveness of 29.0% (95% CI, 11.3% to 43.1%). The total effectiveness of HRV against ARD among vaccinees was 41.4% (95% CI, 23.2% to 55.2%). The point estimate for total effectiveness was higher against ARD during the first year of life than during the second (45.2% versus 28.9%), but estimates for the second year of life lacked precision and did not reach statistical significance. Indirect effects were not detected. To check for bias in presentation to treatment facilities, we evaluated the effectiveness of HRV against acute diarrhea associated with enterotoxigenic Escherichia coli; it was 4.0% (95% CI, −46.5% to 37.1%), indicating that bias likely was not introduced. Thirteen serious adverse events were identified among recipients of HRV, but none were considered related to receipt of study vaccine. The main limitation of this study is that it was an open-label study with an observed-only control group (no placebo). Conclusions: The two-dose HRV rotavirus vaccination program significantly reduced medically attended ARD in this low-resource population in Asia. Protection among vaccinees was similar to that in other low-resource settings. In low-resource populations with high rotavirus incidence, large-scale vaccination across a wide population may be required to obtain the full benefit of rotavirus vaccination, including indirect effects. Trial registration: ClinicalTrials.gov NCT00737503.

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