Four-year efficacy of RTS,S/AS01E and its interaction with malaria exposure.
BACKGROUND: The candidate malaria vaccine RTS,S/AS01E has entered phase 3 trials, but data on long-term outcomes are limited. METHODS: For 4 years, we followed children who had been randomly assigned, at 5 to 17 months of age, to receive three doses of RTS,S/AS01E vaccine (223 children) or rabies va...
| Main Authors: | , , , , , , , , , , , |
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| 格式: | Journal article |
| 语言: | English |
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2013
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| _version_ | 1826295100213297152 |
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| author | Olotu, A Fegan, G Wambua, J Nyangweso, G Awuondo, K Leach, A Lievens, M Leboulleux, D Njuguna, P Peshu, N Marsh, K Bejon, P |
| author_facet | Olotu, A Fegan, G Wambua, J Nyangweso, G Awuondo, K Leach, A Lievens, M Leboulleux, D Njuguna, P Peshu, N Marsh, K Bejon, P |
| author_sort | Olotu, A |
| collection | OXFORD |
| description | BACKGROUND: The candidate malaria vaccine RTS,S/AS01E has entered phase 3 trials, but data on long-term outcomes are limited. METHODS: For 4 years, we followed children who had been randomly assigned, at 5 to 17 months of age, to receive three doses of RTS,S/AS01E vaccine (223 children) or rabies vaccine (224 controls). The end point was clinical malaria (temperature of ≥37.5°C and Plasmodium falciparum parasitemia density of >2500 parasites per cubic millimeter). Each child's exposure to malaria was estimated with the use of the distance-weighted local prevalence of malaria. RESULTS: Over a period of 4 years, 118 of 223 children who received the RTS,S/AS01E vaccine and 138 of 224 of the controls had at least 1 episode of clinical malaria. Vaccine efficacies in the intention-to-treat and per-protocol analyses were 29.9% (95% confidence interval [CI], 10.3 to 45.3; P=0.005) and 32.1% (95% CI, 11.6 to 47.8; P=0.004), respectively, calculated by Cox regression. Multiple episodes were common, with 551 and 618 malarial episodes in the RTS,S/AS01E and control groups, respectively; vaccine efficacies in the intention-to-treat and per-protocol analyses were 16.8% (95% CI, -8.6 to 36.3; P=0.18) and 24.3% (95% CI, 1.9 to 41.6; P=0.04), respectively, calculated by the Andersen-Gill extension of the Cox model. For every 100 vaccinated children, 65 cases of clinical malaria were averted. Vaccine efficacy declined over time (P=0.004) and with increasing exposure to malaria (P=0.001) in the per-protocol analysis. Vaccine efficacy was 43.6% (95% CI, 15.5 to 62.3) in the first year but was -0.4% (95% CI, -32.1 to 45.3) in the fourth year. Among children with a malaria-exposure index that was average or lower than average, the vaccine efficacy was 45.1% (95% CI, 11.3 to 66.0), but among children with a malaria-exposure index that was higher than average it was 15.9% (95% CI, -11.0 to 36.4). CONCLUSIONS: The efficacy of RTS,S/AS01E vaccine over the 4-year period was 16.8%. Efficacy declined over time and with increasing malaria exposure. (Funded by the PATH Malaria Vaccine Initiative and Wellcome Trust; ClinicalTrials.gov number, NCT00872963.). |
| first_indexed | 2024-03-07T03:55:54Z |
| format | Journal article |
| id | oxford-uuid:c2db2af1-bf4f-41e3-be1e-677bfba5c49d |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:55:54Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | oxford-uuid:c2db2af1-bf4f-41e3-be1e-677bfba5c49d2022-03-27T06:12:04ZFour-year efficacy of RTS,S/AS01E and its interaction with malaria exposure.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c2db2af1-bf4f-41e3-be1e-677bfba5c49dEnglishSymplectic Elements at Oxford2013Olotu, AFegan, GWambua, JNyangweso, GAwuondo, KLeach, ALievens, MLeboulleux, DNjuguna, PPeshu, NMarsh, KBejon, PBACKGROUND: The candidate malaria vaccine RTS,S/AS01E has entered phase 3 trials, but data on long-term outcomes are limited. METHODS: For 4 years, we followed children who had been randomly assigned, at 5 to 17 months of age, to receive three doses of RTS,S/AS01E vaccine (223 children) or rabies vaccine (224 controls). The end point was clinical malaria (temperature of ≥37.5°C and Plasmodium falciparum parasitemia density of >2500 parasites per cubic millimeter). Each child's exposure to malaria was estimated with the use of the distance-weighted local prevalence of malaria. RESULTS: Over a period of 4 years, 118 of 223 children who received the RTS,S/AS01E vaccine and 138 of 224 of the controls had at least 1 episode of clinical malaria. Vaccine efficacies in the intention-to-treat and per-protocol analyses were 29.9% (95% confidence interval [CI], 10.3 to 45.3; P=0.005) and 32.1% (95% CI, 11.6 to 47.8; P=0.004), respectively, calculated by Cox regression. Multiple episodes were common, with 551 and 618 malarial episodes in the RTS,S/AS01E and control groups, respectively; vaccine efficacies in the intention-to-treat and per-protocol analyses were 16.8% (95% CI, -8.6 to 36.3; P=0.18) and 24.3% (95% CI, 1.9 to 41.6; P=0.04), respectively, calculated by the Andersen-Gill extension of the Cox model. For every 100 vaccinated children, 65 cases of clinical malaria were averted. Vaccine efficacy declined over time (P=0.004) and with increasing exposure to malaria (P=0.001) in the per-protocol analysis. Vaccine efficacy was 43.6% (95% CI, 15.5 to 62.3) in the first year but was -0.4% (95% CI, -32.1 to 45.3) in the fourth year. Among children with a malaria-exposure index that was average or lower than average, the vaccine efficacy was 45.1% (95% CI, 11.3 to 66.0), but among children with a malaria-exposure index that was higher than average it was 15.9% (95% CI, -11.0 to 36.4). CONCLUSIONS: The efficacy of RTS,S/AS01E vaccine over the 4-year period was 16.8%. Efficacy declined over time and with increasing malaria exposure. (Funded by the PATH Malaria Vaccine Initiative and Wellcome Trust; ClinicalTrials.gov number, NCT00872963.). |
| spellingShingle | Olotu, A Fegan, G Wambua, J Nyangweso, G Awuondo, K Leach, A Lievens, M Leboulleux, D Njuguna, P Peshu, N Marsh, K Bejon, P Four-year efficacy of RTS,S/AS01E and its interaction with malaria exposure. |
| title | Four-year efficacy of RTS,S/AS01E and its interaction with malaria exposure. |
| title_full | Four-year efficacy of RTS,S/AS01E and its interaction with malaria exposure. |
| title_fullStr | Four-year efficacy of RTS,S/AS01E and its interaction with malaria exposure. |
| title_full_unstemmed | Four-year efficacy of RTS,S/AS01E and its interaction with malaria exposure. |
| title_short | Four-year efficacy of RTS,S/AS01E and its interaction with malaria exposure. |
| title_sort | four year efficacy of rts s as01e and its interaction with malaria exposure |
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