TY - JOUR T1 - Protection by vaccination of children against typhoid fever with a Vi-tetanus toxoid conjugate vaccine in urban Bangladesh: a cluster-randomised trial. AU - Qadri,Firdausi, AU - Khanam,Farhana, AU - Liu,Xinxue, AU - Theiss-Nyland,Katherine, AU - Biswas,Prasanta Kumar, AU - Bhuiyan,Amirul Islam, AU - Ahmmed,Faisal, AU - Colin-Jones,Rachel, AU - Smith,Nicola, AU - Tonks,Susan, AU - Voysey,Merryn, AU - Mujadidi,Yama F, AU - Mazur,Olga, AU - Rajib,Nazmul Hasan, AU - Hossen,Md Ismail, AU - Ahmed,Shams Uddin, AU - Khan,Arifuzzaman, AU - Rahman,Nazia, AU - Babu,Golap, AU - Greenland,Melanie, AU - Kelly,Sarah, AU - Ireen,Mahzabeen, AU - Islam,Kamrul, AU - O'Reilly,Peter, AU - Scherrer,Karin Sofia, AU - Pitzer,Virginia E, AU - Neuzil,Kathleen M, AU - Zaman,K, AU - Pollard,Andrew J, AU - Clemens,John D, Y1 - 2021/08/09/ PY - 2021/02/03/received PY - 2021/05/07/revised PY - 2021/05/10/accepted PY - 2021/8/14/pubmed PY - 2021/9/18/medline PY - 2021/8/13/entrez SP - 675 EP - 684 JF - Lancet (London, England) JO - Lancet VL - 398 IS - 10301 N2 - BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: The study was funded by the Bill & Melinda Gates Foundation. SN - 1474-547X UR - https://www.unboundmedicine.com/medline/citation/34384540/Protection_by_vaccination_of_children_against_typhoid_fever_with_a_Vi_tetanus_toxoid_conjugate_vaccine_in_urban_Bangladesh:_a_cluster_randomised_trial_ DB - PRIME DP - Unbound Medicine ER -