Efficacy of typhoid conjugate vaccine in Nepal: final results of a phase 3, randomised, controlled trial

Mila Shakya, MPH; Merryn Voysey, DPhil; Katherine Theiss-Nyland, PhD; Rachel Colin-Jones, MA; Dikshya Pant, FCPS; Anup Adhikari, MA; Susan Tonks, BSc; Yama F Mujadidi, MSc; Peter O’Reilly, MBBCh; Olga Mazur, MSc; Sarah Kelly, MSc; Xinxue Liu, PhD; Archana Maharjan, MA; Ashata Dahal, MPH; Naheeda Haque, PharmD; Anisha Pradhan, BSc; Suchita Shrestha, MPH; Manij Joshi, BPharm; Nicola Smith, MBBCh; Jennifer Hill, PhD; Jenny Clarke, PhD; Lisa Stockdale, PhD; Elizabeth Jones, BMedSc; Timothy Lubinda, MSc; Binod Bajracharya, MD; Sabina Dongol, DPhil; Abhilasha Karkey, DPhil; Stephen Baker, ProfPhD; Gordan Dougan, ProfPhD; Virginia E Pitzer, ScD; Kathleen M Neuzil, ProfMD; Shrijana Shrestha, ProfMD; Buddha Basnyat, ProfFRCPE; Andrew J Pollard, ProfFMedSci

The Lancet Global Health (Nov 2021)

Efficacy of typhoid conjugate vaccine in Nepal: final results of a phase 3, randomised, controlled trial

Mila Shakya, MPH,
Merryn Voysey, DPhil,
Katherine Theiss-Nyland, PhD,
Rachel Colin-Jones, MA,
Dikshya Pant, FCPS,
Anup Adhikari, MA,
Susan Tonks, BSc,
Yama F Mujadidi, MSc,
Peter O’Reilly, MBBCh,
Olga Mazur, MSc,
Sarah Kelly, MSc,
Xinxue Liu, PhD,
Archana Maharjan, MA,
Ashata Dahal, MPH,
Naheeda Haque, PharmD,
Anisha Pradhan, BSc,
Suchita Shrestha, MPH,
Manij Joshi, BPharm,
Nicola Smith, MBBCh,
Jennifer Hill, PhD,
Jenny Clarke, PhD,
Lisa Stockdale, PhD,
Elizabeth Jones, BMedSc,
Timothy Lubinda, MSc,
Binod Bajracharya, MD,
Sabina Dongol, DPhil,
Abhilasha Karkey, DPhil,
Stephen Baker, ProfPhD,
Gordan Dougan, ProfPhD,
Virginia E Pitzer, ScD,
Kathleen M Neuzil, ProfMD,
Shrijana Shrestha, ProfMD,
Buddha Basnyat, ProfFRCPE,
Andrew J Pollard, ProfFMedSci

Affiliations

Mila Shakya, MPH: Oxford University Clinical Research Unit, Patan Academy of Health Sciences, Lalitpur, Nepal; Correspondence to: Dr Mila Shakya, Oxford University Clinical Research Unit, Patan Academy of Health Sciences, Lalitpur, Nepal
Merryn Voysey, DPhil: Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK
Katherine Theiss-Nyland, PhD: Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK
Rachel Colin-Jones, MA: Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK
Dikshya Pant, FCPS: Patan Academy of Health Sciences, Patan Hospital, Lalitpur, Nepal
Anup Adhikari, MA: Nepal Family Development Foundation, Lalitpur, Nepal
Susan Tonks, BSc: Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK
Yama F Mujadidi, MSc: Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK
Peter O’Reilly, MBBCh: Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK
Olga Mazur, MSc: Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK
Sarah Kelly, MSc: Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK
Xinxue Liu, PhD: Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK
Archana Maharjan, MA: Oxford University Clinical Research Unit, Patan Academy of Health Sciences, Lalitpur, Nepal
Ashata Dahal, MPH: Oxford University Clinical Research Unit, Patan Academy of Health Sciences, Lalitpur, Nepal
Naheeda Haque, PharmD: Oxford University Clinical Research Unit, Patan Academy of Health Sciences, Lalitpur, Nepal
Anisha Pradhan, BSc: Oxford University Clinical Research Unit, Patan Academy of Health Sciences, Lalitpur, Nepal
Suchita Shrestha, MPH: Oxford University Clinical Research Unit, Patan Academy of Health Sciences, Lalitpur, Nepal
Manij Joshi, BPharm: Oxford University Clinical Research Unit, Patan Academy of Health Sciences, Lalitpur, Nepal
Nicola Smith, MBBCh: Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK
Jennifer Hill, PhD: Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK
Jenny Clarke, PhD: Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK
Lisa Stockdale, PhD: Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK
Elizabeth Jones, BMedSc: Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK
Timothy Lubinda, MSc: Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK
Binod Bajracharya, MD: Wasa Pasa Polyclinics Private, Lalitpur, Nepal
Sabina Dongol, DPhil: Oxford University Clinical Research Unit, Patan Academy of Health Sciences, Lalitpur, Nepal
Abhilasha Karkey, DPhil: Oxford University Clinical Research Unit, Patan Academy of Health Sciences, Lalitpur, Nepal
Stephen Baker, ProfPhD: Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge, UK
Gordan Dougan, ProfPhD: Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge, UK
Virginia E Pitzer, ScD: Department of Epidemiology of Microbial Diseases, Yale School of Public Health, Yale University, New Haven, CT, USA
Kathleen M Neuzil, ProfMD: School of Medicine, University of Maryland, Baltimore, MD, USA
Shrijana Shrestha, ProfMD: Patan Academy of Health Sciences, Patan Hospital, Lalitpur, Nepal
Buddha Basnyat, ProfFRCPE: Oxford University Clinical Research Unit, Patan Academy of Health Sciences, Lalitpur, Nepal; Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK
Andrew J Pollard, ProfFMedSci: Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK

Journal volume & issue: Vol. 9, no. 11
pp. e1561 – e1568

Abstract

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Summary: Background: Typhoid fever is a major public health problem in low-resource settings. Vaccination can help curb the disease and might reduce transmission. We have previously reported an interim analysis of the efficacy of typhoid conjugate vaccine (TCV) in Nepali children. Here we report the final results after 2 years of follow-up. Methods: We did a participant-masked and observer-masked individually randomised trial in Lalitpur, Nepal, in which 20 019 children aged 9 months to younger than 16 years were randomly assigned in a 1:1 ratio to receive a single dose of TCV (Typbar TCV, Bharat Biotech International, India) or capsular group A meningococcal conjugate vaccine (MenA). Participants were followed up until April 9, 2020. The primary outcome was blood culture-confirmed typhoid fever. Cases were captured via passive surveillance and active telephone surveillance followed by medical record review. The trial is registered at ISRCTN registry, ISRCTN43385161 and is ongoing. Findings: From Nov 20, 2017, to April 9, 2018, of 20 119 children screened, 20 019 participants were randomly assigned to receive TCV or MenA vaccine. There were 75 cases of blood culture-confirmed typhoid fever included in the analysis (13 in the TCV group and 62 in the MenA group) over the 2-year period. The protective efficacy of TCV against blood culture-confirmed typhoid fever at 2 years was 79·0% (95% CI 61·9–88·5; p<0·0001). The incidence of typhoid fever was 72 (95% CI 38–123) cases per 100 000 person-years in the TCV group and 342 (95% CI 262–438) cases per 100 000 person-years in the MenA group. Adverse events occurring within the first 7 days post-vaccination were reported previously. Interpretation: The final results of this randomised, controlled trial are in keeping with the results of our published interim analysis. There is no evidence of waning protection over a 2-year period. These findings add further support for the WHO recommendations on control of enteric fever. Funding: Bill & Melinda Gates Foundation.

Published in The Lancet Global Health

ISSN: 2214-109X (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Medicine: Public aspects of medicine
Website: http://www.lancet.com/journals/langlo/issue/current

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