Phase 3 efficacy analysis of a typhoid conjugate vaccine trial in Nepal
<p><strong>BACKGROUND</strong></p> <p>Salmonella Typhi is a major cause of fever in children in low- and middle-income countries. A typhoid conjugate vaccine (TCV) that was recently prequalified by the World Health Organization was shown to be efficacious in a human cha...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Massachusetts Medical Society
2019
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| _version_ | 1826297896829452288 |
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| author | Shakya, M Colin-Jones, R Theiss-Nyland, K Voysey, M Pant, D Smith, N Liu, X Tonks, S Mazur, O Farooq, YG Clarke, J Hill, J Adhikari, A Dongol, S Karkey, A Bajracharya, B Kelly, S Gurung, M Baker, S Neuzil, KM Shrestha, S Basnyat, B Pollard, AJ Tyvac Nepal Study Team |
| author_facet | Shakya, M Colin-Jones, R Theiss-Nyland, K Voysey, M Pant, D Smith, N Liu, X Tonks, S Mazur, O Farooq, YG Clarke, J Hill, J Adhikari, A Dongol, S Karkey, A Bajracharya, B Kelly, S Gurung, M Baker, S Neuzil, KM Shrestha, S Basnyat, B Pollard, AJ Tyvac Nepal Study Team |
| author_sort | Shakya, M |
| collection | OXFORD |
| description | <p><strong>BACKGROUND</strong></p> <p>Salmonella Typhi is a major cause of fever in children in low- and middle-income countries. A typhoid conjugate vaccine (TCV) that was recently prequalified by the World Health Organization was shown to be efficacious in a human challenge model, but data from efficacy trials in areas where typhoid is endemic are lacking.</p> <p><strong>METHODS</strong></p> <p>In this phase 3, randomized, controlled trial in Lalitpur, Nepal, in which both the participants and observers were unaware of the trial-group assignments, we randomly assigned children who were between 9 months and 16 years of age, in a 1:1 ratio, to receive either a TCV or a capsular group A meningococcal conjugate vaccine (MenA) as a control. The primary outcome was typhoid fever confirmed by blood culture. We present the prespecified analysis of the primary and main secondary outcomes (including an immunogenicity subgroup); the 2-year trial follow-up is ongoing.</p> <p><strong>RESULTS</strong></p> <p>A total of 10,005 participants received the TCV and 10,014 received the MenA vaccine. Blood culture–confirmed typhoid fever occurred in 7 participants who received TCV (79 cases per 100,000 person-years) and in 38 who received MenA vaccine (428 cases per 100,000 person-years) (vaccine efficacy, 81.6%; 95% confidence interval, 58.8 to 91.8; P<0.001). A total of 132 serious adverse events (61 in the TCV group and 71 in the MenA vaccine group) occurred in the first 6 months, and 1 event (pyrexia) was identified as being vaccine-related; the participant remained unaware of the trial-group assignment. Similar rates of adverse events were noted in the two trial groups; fever developed in 5.0% of participants in the TCV group and 5.4% in the MenA vaccine group in the first week after vaccination. In the immunogenicity subgroup, seroconversion (a Vi IgG level that at least quadrupled 28 days after vaccination) was 99% in the TCV group (677 of 683 participants) and 2% in the MenA vaccine group (8 of 380 participants).</p> <p><strong>CONCLUSIONS</strong></p> <p>A single dose of TCV was immunogenic and effective in reducing S. Typhi bacteremia in children 9 months to 16 years of age. (Funded by the Bill and Melinda Gates Foundation; Current Controlled Trials number, ISRCTN43385161. opens in new tab.)</p> |
| first_indexed | 2024-03-07T04:38:37Z |
| format | Journal article |
| id | oxford-uuid:d0d7fd44-046d-42a5-9af7-dd3353c9c721 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:38:37Z |
| publishDate | 2019 |
| publisher | Massachusetts Medical Society |
| record_format | dspace |
| spelling | oxford-uuid:d0d7fd44-046d-42a5-9af7-dd3353c9c7212022-03-27T07:52:59ZPhase 3 efficacy analysis of a typhoid conjugate vaccine trial in NepalJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d0d7fd44-046d-42a5-9af7-dd3353c9c721EnglishSymplectic Elements at OxfordMassachusetts Medical Society2019Shakya, MColin-Jones, RTheiss-Nyland, KVoysey, MPant, DSmith, NLiu, XTonks, SMazur, OFarooq, YGClarke, JHill, JAdhikari, ADongol, SKarkey, ABajracharya, BKelly, SGurung, MBaker, SNeuzil, KMShrestha, SBasnyat, BPollard, AJTyvac Nepal Study Team<p><strong>BACKGROUND</strong></p> <p>Salmonella Typhi is a major cause of fever in children in low- and middle-income countries. A typhoid conjugate vaccine (TCV) that was recently prequalified by the World Health Organization was shown to be efficacious in a human challenge model, but data from efficacy trials in areas where typhoid is endemic are lacking.</p> <p><strong>METHODS</strong></p> <p>In this phase 3, randomized, controlled trial in Lalitpur, Nepal, in which both the participants and observers were unaware of the trial-group assignments, we randomly assigned children who were between 9 months and 16 years of age, in a 1:1 ratio, to receive either a TCV or a capsular group A meningococcal conjugate vaccine (MenA) as a control. The primary outcome was typhoid fever confirmed by blood culture. We present the prespecified analysis of the primary and main secondary outcomes (including an immunogenicity subgroup); the 2-year trial follow-up is ongoing.</p> <p><strong>RESULTS</strong></p> <p>A total of 10,005 participants received the TCV and 10,014 received the MenA vaccine. Blood culture–confirmed typhoid fever occurred in 7 participants who received TCV (79 cases per 100,000 person-years) and in 38 who received MenA vaccine (428 cases per 100,000 person-years) (vaccine efficacy, 81.6%; 95% confidence interval, 58.8 to 91.8; P<0.001). A total of 132 serious adverse events (61 in the TCV group and 71 in the MenA vaccine group) occurred in the first 6 months, and 1 event (pyrexia) was identified as being vaccine-related; the participant remained unaware of the trial-group assignment. Similar rates of adverse events were noted in the two trial groups; fever developed in 5.0% of participants in the TCV group and 5.4% in the MenA vaccine group in the first week after vaccination. In the immunogenicity subgroup, seroconversion (a Vi IgG level that at least quadrupled 28 days after vaccination) was 99% in the TCV group (677 of 683 participants) and 2% in the MenA vaccine group (8 of 380 participants).</p> <p><strong>CONCLUSIONS</strong></p> <p>A single dose of TCV was immunogenic and effective in reducing S. Typhi bacteremia in children 9 months to 16 years of age. (Funded by the Bill and Melinda Gates Foundation; Current Controlled Trials number, ISRCTN43385161. opens in new tab.)</p> |
| spellingShingle | Shakya, M Colin-Jones, R Theiss-Nyland, K Voysey, M Pant, D Smith, N Liu, X Tonks, S Mazur, O Farooq, YG Clarke, J Hill, J Adhikari, A Dongol, S Karkey, A Bajracharya, B Kelly, S Gurung, M Baker, S Neuzil, KM Shrestha, S Basnyat, B Pollard, AJ Tyvac Nepal Study Team Phase 3 efficacy analysis of a typhoid conjugate vaccine trial in Nepal |
| title | Phase 3 efficacy analysis of a typhoid conjugate vaccine trial in Nepal |
| title_full | Phase 3 efficacy analysis of a typhoid conjugate vaccine trial in Nepal |
| title_fullStr | Phase 3 efficacy analysis of a typhoid conjugate vaccine trial in Nepal |
| title_full_unstemmed | Phase 3 efficacy analysis of a typhoid conjugate vaccine trial in Nepal |
| title_short | Phase 3 efficacy analysis of a typhoid conjugate vaccine trial in Nepal |
| title_sort | phase 3 efficacy analysis of a typhoid conjugate vaccine trial in nepal |
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