Could Less Be More? Accounting for Fractional-Dose Regimens and Different Number of Vaccine Doses When Measuring the Impact of the RTS,S/AS01E Malaria Vaccine
Abstract Background The RTS,S/AS01E (RTS,S) malaria vaccine is recommended for children in malaria endemic areas. This phase 2b trial evaluates RTS,S fractional- and full-dose regimens in Ghana and Kenya. Methods In total, 1500 children aged 5–17 months were randomized (1:1:1:1:1) to receive RTS,S o...
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| Veröffentlicht in: | The Journal of infectious diseases 2024-08, Vol.230 (2), p.e486-e495 |
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| creator | Westercamp, Nelli Osei-Tutu, Lawrence Schuerman, Lode Kariuki, Simon K Bollaerts, Anne Lee, Cynthia K Samuels, Aaron M Ockenhouse, Christian Bii, Dennis K Adjei, Samuel Oneko, Martina Lievens, Marc Attobrah Sarfo, Maame Anima Atieno, Cecilia Bakari, Ashura Sang, Tony Kotoh-Mortty, Maame Fremah Otieno, Kephas Roman, François Buabeng, Patrick Boakye Yiadom Ntiamoah, Yaw Ansong, Daniel Agbenyega, Tsiri Ofori-Anyinam, Opokua |
| description | Abstract
Background
The RTS,S/AS01E (RTS,S) malaria vaccine is recommended for children in malaria endemic areas. This phase 2b trial evaluates RTS,S fractional- and full-dose regimens in Ghana and Kenya.
Methods
In total, 1500 children aged 5–17 months were randomized (1:1:1:1:1) to receive RTS,S or rabies control vaccine. RTS,S groups received 2 full RTS,S doses at months 0 and 1 and either full (groups R012-20, R012-14-26) or fractional doses (one-fifth; groups Fx012-14-26, Fx017-20-32).
Results
At month 32 post-dose 1, vaccine efficacy against clinical malaria (all episodes) ranged from 38% (R012-20; 95% confidence interval [CI]: 24%–49%) to 53% (R012-14-26; 95% CI: 42%–62%). Vaccine impact (cumulative number of cases averted/1000 children vaccinated) was 1344 (R012-20), 2450 (R012-14-26), 2273 (Fx012-14-26), and 2112 (Fx017-20-32). To account for differences in vaccine volume (fractional vs full dose; post hoc analysis), we estimated cases averted/1000 RTS,S full-dose equivalents: 336 (R012-20), 490 (R012-14-26), 874 (Fx012-14-26), and 880 (Fx017-20-32).
Conclusions
Vaccine efficacy was similar across RTS,S groups. Vaccine impact accounting for full-dose equivalence suggests that using fractional-dose regimens could be a viable dose-sparing strategy. If maintained through trial end, these observations underscore the means to reduce cost per regimen thus maximizing impact and optimizing supply.
Clinical Trials Registration
NCT03276962 (ClinicalTrials.gov).
Full- and fractional-dose regimens of the RTS,S/AS01E malaria vaccine have similar vaccine efficacy against clinical malaria. With a fixed supply of vaccine, more children can be vaccinated and thus more cases prevented by using fractional- rather than full-dose regimens.
The RTS,S/AS01E (RTS,S) malaria vaccine is currently the only malaria vaccine recommended for use in children from areas with moderate to high risk of malaria. We are conducting a trial in children in Ghana and Kenya to compare regimens with the third and subsequent RTS,S doses reduced to one-fifth and/or delayed vs the standard regimen, full-dose regimens, and a control vaccine. While we did not demonstrate superior vaccine efficacy of fractional- vs full-dose regimens, we showed that all RTS,S regimens provided substantial protection against malaria and were immunogenic and well tolerated during 32 months from the first RTS,S dose. We also calculated vaccine impact, measured as the number of malaria cases prevented for each 1000 c |
| doi_str_mv | 10.1093/infdis/jiae075 |
| format | Article |
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Background
The RTS,S/AS01E (RTS,S) malaria vaccine is recommended for children in malaria endemic areas. This phase 2b trial evaluates RTS,S fractional- and full-dose regimens in Ghana and Kenya.
Methods
In total, 1500 children aged 5–17 months were randomized (1:1:1:1:1) to receive RTS,S or rabies control vaccine. RTS,S groups received 2 full RTS,S doses at months 0 and 1 and either full (groups R012-20, R012-14-26) or fractional doses (one-fifth; groups Fx012-14-26, Fx017-20-32).
Results
At month 32 post-dose 1, vaccine efficacy against clinical malaria (all episodes) ranged from 38% (R012-20; 95% confidence interval [CI]: 24%–49%) to 53% (R012-14-26; 95% CI: 42%–62%). Vaccine impact (cumulative number of cases averted/1000 children vaccinated) was 1344 (R012-20), 2450 (R012-14-26), 2273 (Fx012-14-26), and 2112 (Fx017-20-32). To account for differences in vaccine volume (fractional vs full dose; post hoc analysis), we estimated cases averted/1000 RTS,S full-dose equivalents: 336 (R012-20), 490 (R012-14-26), 874 (Fx012-14-26), and 880 (Fx017-20-32).
Conclusions
Vaccine efficacy was similar across RTS,S groups. Vaccine impact accounting for full-dose equivalence suggests that using fractional-dose regimens could be a viable dose-sparing strategy. If maintained through trial end, these observations underscore the means to reduce cost per regimen thus maximizing impact and optimizing supply.
Clinical Trials Registration
NCT03276962 (ClinicalTrials.gov).
Full- and fractional-dose regimens of the RTS,S/AS01E malaria vaccine have similar vaccine efficacy against clinical malaria. With a fixed supply of vaccine, more children can be vaccinated and thus more cases prevented by using fractional- rather than full-dose regimens.
The RTS,S/AS01E (RTS,S) malaria vaccine is currently the only malaria vaccine recommended for use in children from areas with moderate to high risk of malaria. We are conducting a trial in children in Ghana and Kenya to compare regimens with the third and subsequent RTS,S doses reduced to one-fifth and/or delayed vs the standard regimen, full-dose regimens, and a control vaccine. While we did not demonstrate superior vaccine efficacy of fractional- vs full-dose regimens, we showed that all RTS,S regimens provided substantial protection against malaria and were immunogenic and well tolerated during 32 months from the first RTS,S dose. We also calculated vaccine impact, measured as the number of malaria cases prevented for each 1000 children vaccinated with RTS,S vs the control vaccine. Up to study month 32, we found no systematic differences between full- and fractional-dose RTS,S regimens. However, children receiving fractional doses receive less vaccine. Therefore, we also estimated the number of malaria cases prevented by 1000 RTS,S full doses. We found that fractional-dose regimens can prevent a higher number of cases for the same volume of vaccine administered. These findings suggest that fractional RTS,S doses could be used to improve the impact of the malaria vaccine program with the available vaccine supply.</description><identifier>ISSN: 0022-1899</identifier><identifier>ISSN: 1537-6613</identifier><identifier>EISSN: 1537-6613</identifier><identifier>DOI: 10.1093/infdis/jiae075</identifier><identifier>PMID: 38438123</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Children ; Clinical trials ; Female ; Ghana ; Humans ; Immunization Schedule ; Infant ; Kenya ; Major ; Malaria ; Malaria - prevention & control ; Malaria Vaccines - administration & dosage ; Malaria Vaccines - immunology ; Malaria, Falciparum - epidemiology ; Malaria, Falciparum - prevention & control ; Male ; Plasmodium falciparum - immunology ; Rabies ; Tropical diseases ; Vaccine Efficacy ; Vaccines</subject><ispartof>The Journal of infectious diseases, 2024-08, Vol.230 (2), p.e486-e495</ispartof><rights>The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. 2024</rights><rights>The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c338t-4434d8322edda476245648cffe358413944a4659358cee48389aaf21a219e5c3</cites><orcidid>0000-0003-0136-9750</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,1578,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38438123$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Westercamp, Nelli</creatorcontrib><creatorcontrib>Osei-Tutu, Lawrence</creatorcontrib><creatorcontrib>Schuerman, Lode</creatorcontrib><creatorcontrib>Kariuki, Simon K</creatorcontrib><creatorcontrib>Bollaerts, Anne</creatorcontrib><creatorcontrib>Lee, Cynthia K</creatorcontrib><creatorcontrib>Samuels, Aaron M</creatorcontrib><creatorcontrib>Ockenhouse, Christian</creatorcontrib><creatorcontrib>Bii, Dennis K</creatorcontrib><creatorcontrib>Adjei, Samuel</creatorcontrib><creatorcontrib>Oneko, Martina</creatorcontrib><creatorcontrib>Lievens, Marc</creatorcontrib><creatorcontrib>Attobrah Sarfo, Maame Anima</creatorcontrib><creatorcontrib>Atieno, Cecilia</creatorcontrib><creatorcontrib>Bakari, Ashura</creatorcontrib><creatorcontrib>Sang, Tony</creatorcontrib><creatorcontrib>Kotoh-Mortty, Maame Fremah</creatorcontrib><creatorcontrib>Otieno, Kephas</creatorcontrib><creatorcontrib>Roman, François</creatorcontrib><creatorcontrib>Buabeng, Patrick Boakye Yiadom</creatorcontrib><creatorcontrib>Ntiamoah, Yaw</creatorcontrib><creatorcontrib>Ansong, Daniel</creatorcontrib><creatorcontrib>Agbenyega, Tsiri</creatorcontrib><creatorcontrib>Ofori-Anyinam, Opokua</creatorcontrib><title>Could Less Be More? Accounting for Fractional-Dose Regimens and Different Number of Vaccine Doses When Measuring the Impact of the RTS,S/AS01E Malaria Vaccine</title><title>The Journal of infectious diseases</title><addtitle>J Infect Dis</addtitle><description>Abstract
Background
The RTS,S/AS01E (RTS,S) malaria vaccine is recommended for children in malaria endemic areas. This phase 2b trial evaluates RTS,S fractional- and full-dose regimens in Ghana and Kenya.
Methods
In total, 1500 children aged 5–17 months were randomized (1:1:1:1:1) to receive RTS,S or rabies control vaccine. RTS,S groups received 2 full RTS,S doses at months 0 and 1 and either full (groups R012-20, R012-14-26) or fractional doses (one-fifth; groups Fx012-14-26, Fx017-20-32).
Results
At month 32 post-dose 1, vaccine efficacy against clinical malaria (all episodes) ranged from 38% (R012-20; 95% confidence interval [CI]: 24%–49%) to 53% (R012-14-26; 95% CI: 42%–62%). Vaccine impact (cumulative number of cases averted/1000 children vaccinated) was 1344 (R012-20), 2450 (R012-14-26), 2273 (Fx012-14-26), and 2112 (Fx017-20-32). To account for differences in vaccine volume (fractional vs full dose; post hoc analysis), we estimated cases averted/1000 RTS,S full-dose equivalents: 336 (R012-20), 490 (R012-14-26), 874 (Fx012-14-26), and 880 (Fx017-20-32).
Conclusions
Vaccine efficacy was similar across RTS,S groups. Vaccine impact accounting for full-dose equivalence suggests that using fractional-dose regimens could be a viable dose-sparing strategy. If maintained through trial end, these observations underscore the means to reduce cost per regimen thus maximizing impact and optimizing supply.
Clinical Trials Registration
NCT03276962 (ClinicalTrials.gov).
Full- and fractional-dose regimens of the RTS,S/AS01E malaria vaccine have similar vaccine efficacy against clinical malaria. With a fixed supply of vaccine, more children can be vaccinated and thus more cases prevented by using fractional- rather than full-dose regimens.
The RTS,S/AS01E (RTS,S) malaria vaccine is currently the only malaria vaccine recommended for use in children from areas with moderate to high risk of malaria. We are conducting a trial in children in Ghana and Kenya to compare regimens with the third and subsequent RTS,S doses reduced to one-fifth and/or delayed vs the standard regimen, full-dose regimens, and a control vaccine. While we did not demonstrate superior vaccine efficacy of fractional- vs full-dose regimens, we showed that all RTS,S regimens provided substantial protection against malaria and were immunogenic and well tolerated during 32 months from the first RTS,S dose. We also calculated vaccine impact, measured as the number of malaria cases prevented for each 1000 children vaccinated with RTS,S vs the control vaccine. Up to study month 32, we found no systematic differences between full- and fractional-dose RTS,S regimens. However, children receiving fractional doses receive less vaccine. Therefore, we also estimated the number of malaria cases prevented by 1000 RTS,S full doses. We found that fractional-dose regimens can prevent a higher number of cases for the same volume of vaccine administered. These findings suggest that fractional RTS,S doses could be used to improve the impact of the malaria vaccine program with the available vaccine supply.</description><subject>Children</subject><subject>Clinical trials</subject><subject>Female</subject><subject>Ghana</subject><subject>Humans</subject><subject>Immunization Schedule</subject><subject>Infant</subject><subject>Kenya</subject><subject>Major</subject><subject>Malaria</subject><subject>Malaria - prevention & control</subject><subject>Malaria Vaccines - administration & dosage</subject><subject>Malaria Vaccines - immunology</subject><subject>Malaria, Falciparum - epidemiology</subject><subject>Malaria, Falciparum - prevention & control</subject><subject>Male</subject><subject>Plasmodium falciparum - immunology</subject><subject>Rabies</subject><subject>Tropical diseases</subject><subject>Vaccine Efficacy</subject><subject>Vaccines</subject><issn>0022-1899</issn><issn>1537-6613</issn><issn>1537-6613</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>TOX</sourceid><sourceid>EIF</sourceid><recordid>eNqFkU1vEzEQhi0EoqFw5YgscQGJbWyP9-tUhbSFSglITQRHy_XOJo527dTerdQ_w29lV0kr4MJpNJrHj2b8EvKWszPOSphaV1c2TndWI8vTZ2TCU8iTLOPwnEwYEyLhRVmekFcx7hhjErL8JTmBQkLBBUzIr7nvm4ouMEb6GenSBzynM2N87zrrNrT2gV4FbTrrnW6SCx-R3uDGtugi1a6iF7auMaDr6Le-vcVAfU1_aGOsQzrSkf7coqNL1LEPo7HbIr1u94NyRMfuZr36tJrOVoxf0qVudLD6UfGavKh1E_HNsZ6S9dXlev41WXz_cj2fLRIDUHSJlCCrAoTAqtIyz4RMM1mYYTNIC8mhlFLLLC2HziDKAopS61pwLXiJqYFTcn7Q7vvbFisznBN0o_bBtjo8KK-t-nvi7FZt_L3iHERWAB8MH46G4O96jJ1qbTTYNNqh76MSJeQ5Y2U5ou__QXe-D8PvRgWcAUsz4CN1dqBM8DEGrJ-24UyN0atD9OoY_fDg3Z83POGPWQ_AxwPg-_3_ZL8B6vu56A</recordid><startdate>20240816</startdate><enddate>20240816</enddate><creator>Westercamp, Nelli</creator><creator>Osei-Tutu, Lawrence</creator><creator>Schuerman, Lode</creator><creator>Kariuki, Simon K</creator><creator>Bollaerts, Anne</creator><creator>Lee, Cynthia K</creator><creator>Samuels, Aaron M</creator><creator>Ockenhouse, Christian</creator><creator>Bii, Dennis K</creator><creator>Adjei, Samuel</creator><creator>Oneko, Martina</creator><creator>Lievens, Marc</creator><creator>Attobrah Sarfo, Maame Anima</creator><creator>Atieno, Cecilia</creator><creator>Bakari, Ashura</creator><creator>Sang, Tony</creator><creator>Kotoh-Mortty, Maame Fremah</creator><creator>Otieno, Kephas</creator><creator>Roman, François</creator><creator>Buabeng, Patrick Boakye Yiadom</creator><creator>Ntiamoah, Yaw</creator><creator>Ansong, Daniel</creator><creator>Agbenyega, Tsiri</creator><creator>Ofori-Anyinam, Opokua</creator><general>Oxford University Press</general><scope>TOX</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-0136-9750</orcidid></search><sort><creationdate>20240816</creationdate><title>Could Less Be More? Accounting for Fractional-Dose Regimens and Different Number of Vaccine Doses When Measuring the Impact of the RTS,S/AS01E Malaria Vaccine</title><author>Westercamp, Nelli ; Osei-Tutu, Lawrence ; Schuerman, Lode ; Kariuki, Simon K ; Bollaerts, Anne ; Lee, Cynthia K ; Samuels, Aaron M ; Ockenhouse, Christian ; Bii, Dennis K ; Adjei, Samuel ; Oneko, Martina ; Lievens, Marc ; Attobrah Sarfo, Maame Anima ; Atieno, Cecilia ; Bakari, Ashura ; Sang, Tony ; Kotoh-Mortty, Maame Fremah ; Otieno, Kephas ; Roman, François ; Buabeng, Patrick Boakye Yiadom ; Ntiamoah, Yaw ; Ansong, Daniel ; Agbenyega, Tsiri ; Ofori-Anyinam, Opokua</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c338t-4434d8322edda476245648cffe358413944a4659358cee48389aaf21a219e5c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Children</topic><topic>Clinical trials</topic><topic>Female</topic><topic>Ghana</topic><topic>Humans</topic><topic>Immunization Schedule</topic><topic>Infant</topic><topic>Kenya</topic><topic>Major</topic><topic>Malaria</topic><topic>Malaria - prevention & control</topic><topic>Malaria Vaccines - administration & dosage</topic><topic>Malaria Vaccines - immunology</topic><topic>Malaria, Falciparum - epidemiology</topic><topic>Malaria, Falciparum - prevention & control</topic><topic>Male</topic><topic>Plasmodium falciparum - immunology</topic><topic>Rabies</topic><topic>Tropical diseases</topic><topic>Vaccine Efficacy</topic><topic>Vaccines</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Westercamp, Nelli</creatorcontrib><creatorcontrib>Osei-Tutu, Lawrence</creatorcontrib><creatorcontrib>Schuerman, Lode</creatorcontrib><creatorcontrib>Kariuki, Simon K</creatorcontrib><creatorcontrib>Bollaerts, Anne</creatorcontrib><creatorcontrib>Lee, Cynthia K</creatorcontrib><creatorcontrib>Samuels, Aaron M</creatorcontrib><creatorcontrib>Ockenhouse, Christian</creatorcontrib><creatorcontrib>Bii, Dennis K</creatorcontrib><creatorcontrib>Adjei, Samuel</creatorcontrib><creatorcontrib>Oneko, Martina</creatorcontrib><creatorcontrib>Lievens, Marc</creatorcontrib><creatorcontrib>Attobrah Sarfo, Maame Anima</creatorcontrib><creatorcontrib>Atieno, Cecilia</creatorcontrib><creatorcontrib>Bakari, Ashura</creatorcontrib><creatorcontrib>Sang, Tony</creatorcontrib><creatorcontrib>Kotoh-Mortty, Maame Fremah</creatorcontrib><creatorcontrib>Otieno, Kephas</creatorcontrib><creatorcontrib>Roman, François</creatorcontrib><creatorcontrib>Buabeng, Patrick Boakye Yiadom</creatorcontrib><creatorcontrib>Ntiamoah, Yaw</creatorcontrib><creatorcontrib>Ansong, Daniel</creatorcontrib><creatorcontrib>Agbenyega, Tsiri</creatorcontrib><creatorcontrib>Ofori-Anyinam, Opokua</creatorcontrib><collection>Oxford Journals Open Access Collection</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Westercamp, Nelli</au><au>Osei-Tutu, Lawrence</au><au>Schuerman, Lode</au><au>Kariuki, Simon K</au><au>Bollaerts, Anne</au><au>Lee, Cynthia K</au><au>Samuels, Aaron M</au><au>Ockenhouse, Christian</au><au>Bii, Dennis K</au><au>Adjei, Samuel</au><au>Oneko, Martina</au><au>Lievens, Marc</au><au>Attobrah Sarfo, Maame Anima</au><au>Atieno, Cecilia</au><au>Bakari, Ashura</au><au>Sang, Tony</au><au>Kotoh-Mortty, Maame Fremah</au><au>Otieno, Kephas</au><au>Roman, François</au><au>Buabeng, Patrick Boakye Yiadom</au><au>Ntiamoah, Yaw</au><au>Ansong, Daniel</au><au>Agbenyega, Tsiri</au><au>Ofori-Anyinam, Opokua</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Could Less Be More? Accounting for Fractional-Dose Regimens and Different Number of Vaccine Doses When Measuring the Impact of the RTS,S/AS01E Malaria Vaccine</atitle><jtitle>The Journal of infectious diseases</jtitle><addtitle>J Infect Dis</addtitle><date>2024-08-16</date><risdate>2024</risdate><volume>230</volume><issue>2</issue><spage>e486</spage><epage>e495</epage><pages>e486-e495</pages><issn>0022-1899</issn><issn>1537-6613</issn><eissn>1537-6613</eissn><abstract>Abstract
Background
The RTS,S/AS01E (RTS,S) malaria vaccine is recommended for children in malaria endemic areas. This phase 2b trial evaluates RTS,S fractional- and full-dose regimens in Ghana and Kenya.
Methods
In total, 1500 children aged 5–17 months were randomized (1:1:1:1:1) to receive RTS,S or rabies control vaccine. RTS,S groups received 2 full RTS,S doses at months 0 and 1 and either full (groups R012-20, R012-14-26) or fractional doses (one-fifth; groups Fx012-14-26, Fx017-20-32).
Results
At month 32 post-dose 1, vaccine efficacy against clinical malaria (all episodes) ranged from 38% (R012-20; 95% confidence interval [CI]: 24%–49%) to 53% (R012-14-26; 95% CI: 42%–62%). Vaccine impact (cumulative number of cases averted/1000 children vaccinated) was 1344 (R012-20), 2450 (R012-14-26), 2273 (Fx012-14-26), and 2112 (Fx017-20-32). To account for differences in vaccine volume (fractional vs full dose; post hoc analysis), we estimated cases averted/1000 RTS,S full-dose equivalents: 336 (R012-20), 490 (R012-14-26), 874 (Fx012-14-26), and 880 (Fx017-20-32).
Conclusions
Vaccine efficacy was similar across RTS,S groups. Vaccine impact accounting for full-dose equivalence suggests that using fractional-dose regimens could be a viable dose-sparing strategy. If maintained through trial end, these observations underscore the means to reduce cost per regimen thus maximizing impact and optimizing supply.
Clinical Trials Registration
NCT03276962 (ClinicalTrials.gov).
Full- and fractional-dose regimens of the RTS,S/AS01E malaria vaccine have similar vaccine efficacy against clinical malaria. With a fixed supply of vaccine, more children can be vaccinated and thus more cases prevented by using fractional- rather than full-dose regimens.
The RTS,S/AS01E (RTS,S) malaria vaccine is currently the only malaria vaccine recommended for use in children from areas with moderate to high risk of malaria. We are conducting a trial in children in Ghana and Kenya to compare regimens with the third and subsequent RTS,S doses reduced to one-fifth and/or delayed vs the standard regimen, full-dose regimens, and a control vaccine. While we did not demonstrate superior vaccine efficacy of fractional- vs full-dose regimens, we showed that all RTS,S regimens provided substantial protection against malaria and were immunogenic and well tolerated during 32 months from the first RTS,S dose. We also calculated vaccine impact, measured as the number of malaria cases prevented for each 1000 children vaccinated with RTS,S vs the control vaccine. Up to study month 32, we found no systematic differences between full- and fractional-dose RTS,S regimens. However, children receiving fractional doses receive less vaccine. Therefore, we also estimated the number of malaria cases prevented by 1000 RTS,S full doses. We found that fractional-dose regimens can prevent a higher number of cases for the same volume of vaccine administered. These findings suggest that fractional RTS,S doses could be used to improve the impact of the malaria vaccine program with the available vaccine supply.</abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>38438123</pmid><doi>10.1093/infdis/jiae075</doi><orcidid>https://orcid.org/0000-0003-0136-9750</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-1899 |
| ispartof | The Journal of infectious diseases, 2024-08, Vol.230 (2), p.e486-e495 |
| issn | 0022-1899 1537-6613 1537-6613 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11326831 |
| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE |
| subjects | Children Clinical trials Female Ghana Humans Immunization Schedule Infant Kenya Major Malaria Malaria - prevention & control Malaria Vaccines - administration & dosage Malaria Vaccines - immunology Malaria, Falciparum - epidemiology Malaria, Falciparum - prevention & control Male Plasmodium falciparum - immunology Rabies Tropical diseases Vaccine Efficacy Vaccines |
| title | Could Less Be More? Accounting for Fractional-Dose Regimens and Different Number of Vaccine Doses When Measuring the Impact of the RTS,S/AS01E Malaria Vaccine |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-03T05%3A15%3A48IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Could%20Less%20Be%20More?%20Accounting%20for%20Fractional-Dose%20Regimens%20and%20Different%20Number%20of%20Vaccine%20Doses%20When%20Measuring%20the%20Impact%20of%20the%20RTS,S/AS01E%20Malaria%20Vaccine&rft.jtitle=The%20Journal%20of%20infectious%20diseases&rft.au=Westercamp,%20Nelli&rft.date=2024-08-16&rft.volume=230&rft.issue=2&rft.spage=e486&rft.epage=e495&rft.pages=e486-e495&rft.issn=0022-1899&rft.eissn=1537-6613&rft_id=info:doi/10.1093/infdis/jiae075&rft_dat=%3Cproquest_pubme%3E2937700991%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3103056311&rft_id=info:pmid/38438123&rft_oup_id=10.1093/infdis/jiae075&rfr_iscdi=true |