Protection by vaccination of children against typhoid fever with a Vi-tetanus toxoid conjugate vaccine in urban Bangladesh: a cluster-randomised trial
<p><strong>Background</strong></p> Typhoid fever remains a major cause of morbidity and mortality in low-income and middle-income countries. Vi-tetanus toxoid conjugate vaccine (Vi-TT) is recommended by WHO for implementation in high-burden countries, but there is little evid...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Elsevier
2021
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| _version_ | 1797071602960039936 |
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| author | Qadri, F Khanam, F Liu, X Theiss-Nyland, K Biswas, PK Bhuiyan, AI Ahmmed, F Colin-Jones, R Smith, N Tonks, S Voysey, M Mujadidi, YF Mazur, O Rajib, NH Hossen, MI Ahmed, SU Khan, A Rahman, N Babu, G Greenland, M Kelly, S Ireen, M Islam, K O'Reilly, P Scherrer, KS Pitzer, VE Neuzil, KM Zaman, K Pollard, AJ Clemens, JD |
| author_facet | Qadri, F Khanam, F Liu, X Theiss-Nyland, K Biswas, PK Bhuiyan, AI Ahmmed, F Colin-Jones, R Smith, N Tonks, S Voysey, M Mujadidi, YF Mazur, O Rajib, NH Hossen, MI Ahmed, SU Khan, A Rahman, N Babu, G Greenland, M Kelly, S Ireen, M Islam, K O'Reilly, P Scherrer, KS Pitzer, VE Neuzil, KM Zaman, K Pollard, AJ Clemens, JD |
| author_sort | Qadri, F |
| collection | OXFORD |
| description | <p><strong>Background</strong></p>
Typhoid fever remains a major cause of morbidity and mortality in low-income and middle-income countries. Vi-tetanus toxoid conjugate vaccine (Vi-TT) is recommended by WHO for implementation in high-burden countries, but there is little evidence about its ability to protect against clinical typhoid in such settings.
<p><strong>Methods</strong></p>
We did a participant-masked and observer-masked cluster-randomised trial preceded by a safety pilot phase in an urban endemic setting in Dhaka, Bangladesh. 150 clusters, each with approximately 1350 residents, were randomly assigned (1:1) to either Vi-TT or SA 14-14-2 Japanese encephalitis (JE) vaccine. Children aged 9 months to less than 16 years were invited via parent or guardian to receive a single, parenteral dose of vaccine according to their cluster of residence. The study population was followed for an average of 17·1 months. Total and overall protection by Vi-TT against blood culture-confirmed typhoid were the primary endpoints assessed in the intention-to-treat population of vaccinees or all residents in the clusters. A subset of approximately 4800 participants was assessed with active surveillance for adverse events. The trial is registered at www.isrctn.com, ISRCTN11643110.
<p><strong>Findings</strong></p>
41 344 children were vaccinated in April–May, 2018, with another 20 412 children vaccinated at catch-up vaccination campaigns between September and December, 2018, and April and May, 2019. The incidence of typhoid fever (cases per 100 000 person-years) was 635 in JE vaccinees and 96 in Vi-TT vaccinees (total Vi-TT protection 85%; 97·5% CI 76 to 91, p<0·0001). Total vaccine protection was consistent in different age groups, including children vaccinated at ages under 2 years (81%; 95% CI 39 to 94, p=0·0052). The incidence was 213 among all residents in the JE clusters and 93 in the Vi-TT clusters (overall Vi-TT protection 57%; 97·5% CI 43 to 68, p<0·0001). We did not observe significant indirect vaccine protection by Vi-TT (19%; 95% CI −12 to 41, p=0·20). The vaccines were well tolerated, and no serious adverse events judged to be vaccine-related were observed.
<p><strong>Interpretation</strong></p>
Vi-TT provided protection against typhoid fever to children vaccinated between 9 months and less than 16 years. Longer-term follow-up will be needed to assess the duration of protection and the need for booster doses.
<p><strong>Funding</strong></p>
The study was funded by the Bill & Melinda Gates Foundation. |
| first_indexed | 2024-03-06T22:55:43Z |
| format | Journal article |
| id | oxford-uuid:604acd6a-f23f-4140-8797-357af554b9c6 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:55:43Z |
| publishDate | 2021 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:604acd6a-f23f-4140-8797-357af554b9c62022-03-26T17:52:37ZProtection by vaccination of children against typhoid fever with a Vi-tetanus toxoid conjugate vaccine in urban Bangladesh: a cluster-randomised trialJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:604acd6a-f23f-4140-8797-357af554b9c6EnglishSymplectic ElementsElsevier2021Qadri, FKhanam, FLiu, XTheiss-Nyland, KBiswas, PKBhuiyan, AIAhmmed, FColin-Jones, RSmith, NTonks, SVoysey, MMujadidi, YFMazur, ORajib, NHHossen, MIAhmed, SUKhan, ARahman, NBabu, GGreenland, MKelly, SIreen, MIslam, KO'Reilly, PScherrer, KSPitzer, VENeuzil, KMZaman, KPollard, AJClemens, JD<p><strong>Background</strong></p> Typhoid fever remains a major cause of morbidity and mortality in low-income and middle-income countries. Vi-tetanus toxoid conjugate vaccine (Vi-TT) is recommended by WHO for implementation in high-burden countries, but there is little evidence about its ability to protect against clinical typhoid in such settings. <p><strong>Methods</strong></p> We did a participant-masked and observer-masked cluster-randomised trial preceded by a safety pilot phase in an urban endemic setting in Dhaka, Bangladesh. 150 clusters, each with approximately 1350 residents, were randomly assigned (1:1) to either Vi-TT or SA 14-14-2 Japanese encephalitis (JE) vaccine. Children aged 9 months to less than 16 years were invited via parent or guardian to receive a single, parenteral dose of vaccine according to their cluster of residence. The study population was followed for an average of 17·1 months. Total and overall protection by Vi-TT against blood culture-confirmed typhoid were the primary endpoints assessed in the intention-to-treat population of vaccinees or all residents in the clusters. A subset of approximately 4800 participants was assessed with active surveillance for adverse events. The trial is registered at www.isrctn.com, ISRCTN11643110. <p><strong>Findings</strong></p> 41 344 children were vaccinated in April–May, 2018, with another 20 412 children vaccinated at catch-up vaccination campaigns between September and December, 2018, and April and May, 2019. The incidence of typhoid fever (cases per 100 000 person-years) was 635 in JE vaccinees and 96 in Vi-TT vaccinees (total Vi-TT protection 85%; 97·5% CI 76 to 91, p<0·0001). Total vaccine protection was consistent in different age groups, including children vaccinated at ages under 2 years (81%; 95% CI 39 to 94, p=0·0052). The incidence was 213 among all residents in the JE clusters and 93 in the Vi-TT clusters (overall Vi-TT protection 57%; 97·5% CI 43 to 68, p<0·0001). We did not observe significant indirect vaccine protection by Vi-TT (19%; 95% CI −12 to 41, p=0·20). The vaccines were well tolerated, and no serious adverse events judged to be vaccine-related were observed. <p><strong>Interpretation</strong></p> Vi-TT provided protection against typhoid fever to children vaccinated between 9 months and less than 16 years. Longer-term follow-up will be needed to assess the duration of protection and the need for booster doses. <p><strong>Funding</strong></p> The study was funded by the Bill & Melinda Gates Foundation. |
| spellingShingle | Qadri, F Khanam, F Liu, X Theiss-Nyland, K Biswas, PK Bhuiyan, AI Ahmmed, F Colin-Jones, R Smith, N Tonks, S Voysey, M Mujadidi, YF Mazur, O Rajib, NH Hossen, MI Ahmed, SU Khan, A Rahman, N Babu, G Greenland, M Kelly, S Ireen, M Islam, K O'Reilly, P Scherrer, KS Pitzer, VE Neuzil, KM Zaman, K Pollard, AJ Clemens, JD Protection by vaccination of children against typhoid fever with a Vi-tetanus toxoid conjugate vaccine in urban Bangladesh: a cluster-randomised trial |
| title | Protection by vaccination of children against typhoid fever with a Vi-tetanus toxoid conjugate vaccine in urban Bangladesh: a cluster-randomised trial |
| title_full | Protection by vaccination of children against typhoid fever with a Vi-tetanus toxoid conjugate vaccine in urban Bangladesh: a cluster-randomised trial |
| title_fullStr | Protection by vaccination of children against typhoid fever with a Vi-tetanus toxoid conjugate vaccine in urban Bangladesh: a cluster-randomised trial |
| title_full_unstemmed | Protection by vaccination of children against typhoid fever with a Vi-tetanus toxoid conjugate vaccine in urban Bangladesh: a cluster-randomised trial |
| title_short | Protection by vaccination of children against typhoid fever with a Vi-tetanus toxoid conjugate vaccine in urban Bangladesh: a cluster-randomised trial |
| title_sort | protection by vaccination of children against typhoid fever with a vi tetanus toxoid conjugate vaccine in urban bangladesh a cluster randomised trial |
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