Tags

Type your tag names separated by a space and hit enter

Protection by vaccination of children against typhoid fever with a Vi-tetanus toxoid conjugate vaccine in urban Bangladesh: a cluster-randomised trial.
Lancet. 2021 08 21; 398(10301):675-684.Lct

Abstract

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.

Authors+Show Affiliations

International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh. Electronic address: fqadri@icddrb.org.International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Oxford, UK.International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh.International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh.International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Oxford, UK.International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh.International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh.International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh.International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh.International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh.International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Oxford, UK.International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh.International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Oxford, UK.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Oxford, UK.Department of Epidemiology of Microbial Diseases, Yale School of Public Health, Yale University, New Haven, CT USA.University of Maryland School of Medicine, Baltimore MD, USA.International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh.Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Oxford, UK.International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh; University of California Los Angeles, Fielding School of Public Health, Los Angeles, CA, USA.

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

34384540

Citation

Qadri, Firdausi, et al. "Protection By Vaccination of Children Against Typhoid Fever With a Vi-tetanus Toxoid Conjugate Vaccine in Urban Bangladesh: a Cluster-randomised Trial." Lancet (London, England), vol. 398, no. 10301, 2021, pp. 675-684.
Qadri F, Khanam F, Liu X, et al. Protection by vaccination of children against typhoid fever with a Vi-tetanus toxoid conjugate vaccine in urban Bangladesh: a cluster-randomised trial. Lancet. 2021;398(10301):675-684.
Qadri, F., Khanam, F., Liu, X., Theiss-Nyland, K., Biswas, P. K., Bhuiyan, A. I., Ahmmed, F., Colin-Jones, R., Smith, N., Tonks, S., Voysey, M., Mujadidi, Y. F., Mazur, O., Rajib, N. H., Hossen, M. I., Ahmed, S. U., Khan, A., Rahman, N., Babu, G., ... Clemens, J. D. (2021). Protection by vaccination of children against typhoid fever with a Vi-tetanus toxoid conjugate vaccine in urban Bangladesh: a cluster-randomised trial. Lancet (London, England), 398(10301), 675-684. https://doi.org/10.1016/S0140-6736(21)01124-7
Qadri F, et al. Protection By Vaccination of Children Against Typhoid Fever With a Vi-tetanus Toxoid Conjugate Vaccine in Urban Bangladesh: a Cluster-randomised Trial. Lancet. 2021 08 21;398(10301):675-684. PubMed PMID: 34384540.
* Article titles in AMA citation format should be in sentence-case
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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0140-6736(21)01124-7 DB - PRIME DP - Unbound Medicine ER -