The public health impact and cost-effectiveness of the R21/Matrix-M malaria vaccine: a mathematical modelling study
<p><strong>Background</strong> The R21/Matrix-M vaccine has demonstrated high efficacy against Plasmodium falciparum clinical malaria in children in sub-Saharan Africa. Using trial data, we aimed to estimate the public health impact and cost-effectiveness of vaccine introduction ac...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Elsevier
2024
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| _version_ | 1811139928169381888 |
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| author | Schmit, N Topazian, HM Natama, HM Bellamy, D Traoré, O Somé, MA Rouamba, T Tahita, MC Bonko, MDA Sourabié, A Sorgho, H Stockdale, L Provstgaard-Morys, S Aboagye, J Woods, D Rapi, K Datoo, MS Ramos Lopez, F Charles, GD McCain, K Ouedraogo, J-B Hamaluba, M Olotu, A Dicko, A Tinto, H Hill, AVS Ewer, KJ Ghani, AC Winskill, P |
| author_facet | Schmit, N Topazian, HM Natama, HM Bellamy, D Traoré, O Somé, MA Rouamba, T Tahita, MC Bonko, MDA Sourabié, A Sorgho, H Stockdale, L Provstgaard-Morys, S Aboagye, J Woods, D Rapi, K Datoo, MS Ramos Lopez, F Charles, GD McCain, K Ouedraogo, J-B Hamaluba, M Olotu, A Dicko, A Tinto, H Hill, AVS Ewer, KJ Ghani, AC Winskill, P |
| author_sort | Schmit, N |
| collection | OXFORD |
| description | <p><strong>Background</strong> The R21/Matrix-M vaccine has demonstrated high efficacy against Plasmodium falciparum clinical malaria in children in sub-Saharan Africa. Using trial data, we aimed to estimate the public health impact and cost-effectiveness of vaccine introduction across sub-Saharan Africa.</p>
<p><strong>Methods</strong> We fitted a semi-mechanistic model of the relationship between anti-circumsporozoite protein antibody titres and vaccine efficacy to data from 3 years of follow-up in the phase 2b trial of R21/Matrix-M in Nanoro, Burkina Faso. We validated the model by comparing predicted vaccine efficacy to that observed over 12–18 months in the phase 3 trial. Integrating this framework within a mathematical transmission model, we estimated the cases, malaria deaths, and disability-adjusted life-years (DALYs) averted and cost-effectiveness over a 15-year time horizon across a range of transmission settings in sub-Saharan Africa. Cost-effectiveness was estimated incorporating the cost of vaccine introduction (dose, consumables, and delivery) relative to existing interventions at baseline. We report estimates at a median of 20% parasite prevalence in children aged 2–10 years (<i>Pf</i>PR<sub>2–10</sub>) and ranges from 3% to 65% <i>Pf</i>PR<sub>2–10</sub>.</p>
<p><strong>Findings</strong> Anti-circumsporozoite protein antibody titres were found to satisfy the criteria for a surrogate of protection for vaccine efficacy against clinical malaria. Age-based implementation of a four-dose regimen of R21/Matrix-M vaccine was estimated to avert 181 825 (range 38 815–333 491) clinical cases per 100 000 fully vaccinated children in perennial settings and 202 017 (29 868–405 702) clinical cases per 100 000 fully vaccinated children in seasonal settings. Similar estimates were obtained for seasonal or hybrid implementation. Under an assumed vaccine dose price of USD 3, the incremental cost per clinical case averted was USD 7 (range 4–48) in perennial settings and USD 6 (3–63) in seasonal settings and the incremental cost per DALY averted was USD 34 (29–139) in perennial settings and USD 30 (22–172) in seasonal settings, with lower cost-effectiveness ratios in settings with higher <i>Pf</i>PR<sub>2–10</sub>.</p>
<p><strong>Interpretation</strong> Introduction of the R21/Matrix-M malaria vaccine could have a substantial public health benefit across sub-Saharan Africa.</p>
<p><strong>Funding</strong> The Wellcome Trust, the Bill & Melinda Gates Foundation, the UK Medical Research Council, the European and Developing Countries Clinical Trials Partnership 2 and 3, the NIHR Oxford Biomedical Research Centre, and the Serum Institute of India, Open Philanthropy.</p> |
| first_indexed | 2024-04-09T03:54:43Z |
| format | Journal article |
| id | oxford-uuid:67c659ad-5e7a-460e-baa9-3917b2ac1f58 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-09-25T04:13:52Z |
| publishDate | 2024 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:67c659ad-5e7a-460e-baa9-3917b2ac1f582024-07-15T10:58:05ZThe public health impact and cost-effectiveness of the R21/Matrix-M malaria vaccine: a mathematical modelling studyJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:67c659ad-5e7a-460e-baa9-3917b2ac1f58EnglishSymplectic ElementsElsevier2024Schmit, NTopazian, HMNatama, HMBellamy, DTraoré, OSomé, MARouamba, TTahita, MCBonko, MDASourabié, ASorgho, HStockdale, LProvstgaard-Morys, SAboagye, JWoods, DRapi, KDatoo, MSRamos Lopez, FCharles, GDMcCain, KOuedraogo, J-BHamaluba, MOlotu, ADicko, ATinto, HHill, AVSEwer, KJGhani, ACWinskill, P<p><strong>Background</strong> The R21/Matrix-M vaccine has demonstrated high efficacy against Plasmodium falciparum clinical malaria in children in sub-Saharan Africa. Using trial data, we aimed to estimate the public health impact and cost-effectiveness of vaccine introduction across sub-Saharan Africa.</p> <p><strong>Methods</strong> We fitted a semi-mechanistic model of the relationship between anti-circumsporozoite protein antibody titres and vaccine efficacy to data from 3 years of follow-up in the phase 2b trial of R21/Matrix-M in Nanoro, Burkina Faso. We validated the model by comparing predicted vaccine efficacy to that observed over 12–18 months in the phase 3 trial. Integrating this framework within a mathematical transmission model, we estimated the cases, malaria deaths, and disability-adjusted life-years (DALYs) averted and cost-effectiveness over a 15-year time horizon across a range of transmission settings in sub-Saharan Africa. Cost-effectiveness was estimated incorporating the cost of vaccine introduction (dose, consumables, and delivery) relative to existing interventions at baseline. We report estimates at a median of 20% parasite prevalence in children aged 2–10 years (<i>Pf</i>PR<sub>2–10</sub>) and ranges from 3% to 65% <i>Pf</i>PR<sub>2–10</sub>.</p> <p><strong>Findings</strong> Anti-circumsporozoite protein antibody titres were found to satisfy the criteria for a surrogate of protection for vaccine efficacy against clinical malaria. Age-based implementation of a four-dose regimen of R21/Matrix-M vaccine was estimated to avert 181 825 (range 38 815–333 491) clinical cases per 100 000 fully vaccinated children in perennial settings and 202 017 (29 868–405 702) clinical cases per 100 000 fully vaccinated children in seasonal settings. Similar estimates were obtained for seasonal or hybrid implementation. Under an assumed vaccine dose price of USD 3, the incremental cost per clinical case averted was USD 7 (range 4–48) in perennial settings and USD 6 (3–63) in seasonal settings and the incremental cost per DALY averted was USD 34 (29–139) in perennial settings and USD 30 (22–172) in seasonal settings, with lower cost-effectiveness ratios in settings with higher <i>Pf</i>PR<sub>2–10</sub>.</p> <p><strong>Interpretation</strong> Introduction of the R21/Matrix-M malaria vaccine could have a substantial public health benefit across sub-Saharan Africa.</p> <p><strong>Funding</strong> The Wellcome Trust, the Bill & Melinda Gates Foundation, the UK Medical Research Council, the European and Developing Countries Clinical Trials Partnership 2 and 3, the NIHR Oxford Biomedical Research Centre, and the Serum Institute of India, Open Philanthropy.</p> |
| spellingShingle | Schmit, N Topazian, HM Natama, HM Bellamy, D Traoré, O Somé, MA Rouamba, T Tahita, MC Bonko, MDA Sourabié, A Sorgho, H Stockdale, L Provstgaard-Morys, S Aboagye, J Woods, D Rapi, K Datoo, MS Ramos Lopez, F Charles, GD McCain, K Ouedraogo, J-B Hamaluba, M Olotu, A Dicko, A Tinto, H Hill, AVS Ewer, KJ Ghani, AC Winskill, P The public health impact and cost-effectiveness of the R21/Matrix-M malaria vaccine: a mathematical modelling study |
| title | The public health impact and cost-effectiveness of the R21/Matrix-M malaria vaccine: a mathematical modelling study |
| title_full | The public health impact and cost-effectiveness of the R21/Matrix-M malaria vaccine: a mathematical modelling study |
| title_fullStr | The public health impact and cost-effectiveness of the R21/Matrix-M malaria vaccine: a mathematical modelling study |
| title_full_unstemmed | The public health impact and cost-effectiveness of the R21/Matrix-M malaria vaccine: a mathematical modelling study |
| title_short | The public health impact and cost-effectiveness of the R21/Matrix-M malaria vaccine: a mathematical modelling study |
| title_sort | public health impact and cost effectiveness of the r21 matrix m malaria vaccine a mathematical modelling study |
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