Last updated: 1 September 2025

Terms of Reference

Full Terms of Reference in PDF format

To formulate critical questions for which an in-depth review of evidence is needed to address current knowledge gaps and issue recommendations for updated programmatic recommendations on the use of  typhoid conjugate vaccines (TCV), and optimisation of the current vaccination schedule, including the need for a booster. Updated recommendations will be submitted for consideration to SAGE to inform the revision of the global policy on typhoid vaccine use, and for subsequent updating the WHO position paper on typhoid vaccines.

In its capacity as an advisory body to WHO, the SAGE WG will be asked to address the following areas in its review:

• Data on the epidemiology and global burden of disease caused by Salmonella Typhi and, specifically, age-stratified data in different geographic regions.
• Evidence of waning immunity linked to vaccination in earlier life to identify:
• Optimal age for administration of the primary dose
• Need and optimal age of administration of a booster dose
• Programmatic feasibility of optimising TCV immunisation schedules to the existing routine immunisation schedules
• Strategies to maximize vaccine uptake (for both: primary and potential booster dose)
• Safety, efficacy and duration of protection evidence conferred by newly WHO prequalified products
• Correlation of population level vaccine effectiveness  with antibody titres (IgG/IgA)
• The economic burden and cost-effectiveness of TCV, including considerations to antimicrobial resistance (AMR)

The SAGE WG will be expected to present the results of the evidence as requested by the WHO

The SAGE WG will be expected to highlight any knowledge gaps and research questions that might require further evidence review and/or the generation of new data through scientific research

Composition

SAGE Members

• Saad Omer: Peter O’Donnell Jr. School of Public Health, UT Southwestern Medical Center, Dallas, United States of America
• Rebecca Grais: Pasteur Network, Paris, France

Experts

• Alejandro Cravioto, Universidad Nacional Autónoma de México, Mexico. 
• John Crump, University of Otago, New Zealand
• Shanta  Dutta, ICMR-National Institute for research in Bacterial Infection (ICMR-NIRBI), India 
• Anelisa  Jaca, South African Medical Research Council, South Africa
• Jacob John. Christian Medical College Vellore, India
• Myron Levine, University of Maryland School of Medicine, USA
• Xinxue  Liu, University of Oxford, United Kingdom
• Virginia Pitzer, Yale School of Public Health, USA
• Firdausi Qadri, International Centre for Diarrhoeal Disease Research, Bangladesh
• Farah Naz Qamar, The Aga University Hospital, Pakistan
• Sodiomon Sirima, Groupe de Recherche Action en santé (GRAS), Burkina Faso
• Richard Strugnell, University Melbourne, Australia

WHO Secretariat

• Christoph Steffen 
• Vinod Bura 
  
• Judith Vanholten 
  

Declaration of interests

All Working Group members completed a declaration of interests. Eight current members reported relevant interests related to the Working Group's terms of reference. It was assessed that all members could fully participate in all proceedings of the Working Group. 

The reported relevant interests are summarized below:

Farah Naz Qamar

• Serves as a COVID-19 vaccine advisory committee on COVAX. This interest was perceived as non-personal, non-specific and financially insignificant*.
• Serves as a Co-Investigator on MRC Wellcome for COVID-19 Prophylaxis Chloroquine versus placebo. This interest was perceived as non-personal, non-specific and financially significant*.
• Serves as Principal Investigator on  Sabin Vaccine Institute  for Immunogenicity and safety of fractional booster dose of COVID-19 vaccines available for use in Pakistan/Brazil: A phase 4 dose-optimizing trial. This interest was perceived as personal, non-specific and financially significant*.
• Serves as Principal Investigator on  Sabin Vaccine Institute  for Azithromycin and cefixime combination versus azithromycin alone for the out-patient treatment of uncomplicated typhoid in South Asia; a randomised controlled trial, this interest was perceived as personal, specific and financially significant*.
• Serves as a as Principal Investigator on Gavi alliance for Assessing introduction and impact of TCV into routine immunization in Gavi-eligible African and Asian countries. This interest was perceived as personal, specific and financially significant*.
• Serves as a Principal Investigator on Bill and Melinda Gates Foundation (BMGF) for  Environmental Surveillance for enteric pathogens in Karachi, Pakistan. This interest was perceived as non-personal, non-specific and financially significant*.
• Serves as a Principal Investigator on The Wellcome Trust  for Azithromycin and cefixime combination versus azithromycin alone for the out-patient treatment of un complicated typhoid in South Asia; a randomised controlled trial. This interest was perceived as non-personal, non-specific and financially significant*.
• Serves as a Principal Investigator on Bill and Melinda Gates Foundation (BMGF)  for Salmonella genomics pre and post-TCV introduction in Pakistan. This interest was perceived as personal, specific and financially significant*.
• Serves as a Principal Investigator on Bill and Melinda Gates Foundation (BMGF) for Enteric for Global Health (EFGH) A shigella surveillance study – Pakistan. This interest was perceived as personal, non-specific and financially significant*.
• Serves as a Principal Investigator on WHO for the Nutritional Management of Moderate Wasting in Children 6-24 months of age with acute illness (NUTRI-MAM Trial). This interest was perceived as non-personal, non-specific and financially significant*.
• Serves as a Principal Investigator on Sabin vaccine institute for Randomized Controlled trial to assess the immunogenicity, safety and reactogenicity of full dose versus fractional dose of Pfizer/BioNTech, AstraZeneca, and Sinovac-CoronaVac COVID-19 vaccines given as an additional dose at least 6 months after full vaccination or PCR-Confirmed infection with SARS-Cov-2 in Healthy Adults. This interest was perceived as personal, non-specific and financially significant*.
• Serves as a Principal Investigator on Bill and Melinda Gates Foundation (BMGF) for TCV - Modelling Project for Typhoid. This interest was perceived as personal, specific and financially insignificant*.
• Serves as a Principal Investigator on Bill and Melinda Gates Foundation (BMGF) for Seroefficacy of typhoid conjugate vaccine in a cohort of children vaccinated in the outbreak in Hyderabad city of Sindh, Pakistan . This interest was perceived as personal, non-specific and financially insignificant*.

 Jacob John

• Serves as a member of the NTAGI (India). This interest was perceived as non-personal, non-specific and financially insignificant*.
• Serves as a chair of the typhoid and cholera working groups. This interest was perceived as non-personal, specific and financially insignificant*.
• Serves as Principal Investigator on the BMGF-funded Typhoid Vaccine Impact Trial. This interest was perceived as non-personal, specific and financially significant*.

  John Andrew Crump

• Serves as a principal Investigator for the following  Bill & Melinda Gates Foundation-funded activities:
  • Research grant, typhoid fever epidemiology data synthesis (TyVAC).
  • Research grant, typhoid fever epidemiology data synthesis (TyVAC 2.0)
  • Research grant, protocol development for NTS transmission study (STRiDENT)
  • Research grant severe typhoid in Tanzania (STT)
  • All of the above interests were perceived as non-personal, specific and financially significant*.
• Received research grant as a principal investigator from Horizon Europe for data synthesis for iNTS disease for GMMA vaccine case (Vacc-iNTS). This interest was perceived as non-personal, non-specific and financially significant*.
• Serves as a co-investigator from WHO on data synthesis on iNTS disease (WHO FERG2). This interest was perceived as non-personal, non-specific and financially significant*.

 Virginia E. Pitzer

• Served until 2023 as a member on the WHO Immunization and Vaccine-related Implementation Research Advisory Committee (IVIR-AC). This interest was perceived as non-personal, non-specific and financially insignificant*.
• Serves as advisor to WHO for WHO Typhoid TPP Development Advisory Group on Typhoid Fever Diagnostic Tests. This interest was perceived as non-personal, specific and financially insignificant*.
• Served until 2024 as advisor to Vaccine Innovation Prioritisation Strategy (VIPS)  (collaboration between Gavi, WHO, UNICEF, BMGF and PATH) for TCV Microarray Patch Full Value of Vaccine Assessment Expert Working Group (Chair). This interest was perceived as non-personal, specific and financially insignificant*.
• Served until 2023 as advisor to WHO for WHO Enteric Burden of Disease Morbidity Expert Working Group. This interest was perceived as non-personal, non-specific and financially insignificant*.
• Serves until 2022 as a member to WHO for WHO Burden of Enteric Fever Expert Working Group. This interest was perceived as non-per sonal, non-specific and financially insignificant*.
• Served as a co-investigator until 2020 on typhoid conjugate vaccine and individual and cluster randomised trials funded by the Bill & Melinda Gates Foundation. This interest was perceived as non-personal, specific, and financially significant*.
• Received until 2023 research grant support from Reckitt Global Hygiene Institute; US CDC for research on climate and diarrhea associations; SARS-CoV-2  transmission patterns. This interest was perceived as non-personal, non-specific and financially significant*.

Dick Strugnell

• Serves as a member of the GSK ad hoc International Adjuvant Advisory Board to prepare materials that help prinary care doctors (esp.) understand the general benefits of vaccination and some of the complexities of modern, adjuvanted vaccines. This interest was perceived as non-personal, non-specific and financially insignificant*.

Myron M. Levine

• Served until 2023 as an external advisory board on Pfizer vaccines to advise on vaccines in development. This interest was perceived as personal, specific and financially significant*.
• Served until 2022 as an advisor for safety review of data for vaccines in trials supported by U.S. Government DSMB overseeing efficacy field trials of COVID-19 vaccines. This interest was perceived as personal, non-specific and financially insignificant*.
• Served until 2022 as an advisor committee on FDA Vaccines & Related Biological Products to advice on vaccines proposed for EUAs or licensure. This interest was perceived as personal, non-specific and financially insignificant*.
• Serves as a member at WHO Technical Advisory Group for Candidate Vaccine Prioritization. This interest was perceived as non-personal, non-specific and infinancially insignificant*.
• Serves at Pfizer History of experimental challenge studies of volunteers to help guide vaccine development. This interest was perceived as personal, non-specific and financially significant*.
• Served until 2023 as a Principal Investigator of a grant and coinvestigator of the clinical Protocol for Wellcome Trust on a Phase 1 trial of a Trivalent Salmonella Conjugate Vaccine (TSCV). This interest was perceived as non-personal, specific, and financially significant*.
• Served until 2024 as a Principal Investigator of a grant and coinvestigator of the clinical Protocol for Wellcome Trust on Phase 1/2A (TSCV). This interest was perceived as non-personal, specific, and financially significant*.
• Serves as Principal Investigator of the grant; Co-investigator of the clinical protocol; Representative of the Sponsor (U. of Maryland Baltimore) of the IND submitted to the U.S. FDA for Wellcome Trust on Phase 2 (TSCV). This interest was perceived as non-personal, specific, and financially significant*.
• Serves as Coinvestigator for MRC-UK on Phase 2 Live oral Salmonella Paratyphi A vaccine. This interest was perceived as non-personal, specific, and financially significant*.
• Intellectual property rights for Bharat Biotech International (BBi), Hyderabad, India on several issued patents based on vaccine research carried out by myself and colleagues at the UMSoM have been licensed for potential future commercialization by BBi for a Trivalent Salmonella Conjugate Vaccine to prevent invasive disease disease caused by Salmonella Enteritidis, S. Typhimurium and S. Typhi; and other patents licensed by BBi relate to the development of a live oral S. Paratyphi A vaccine. This interest was perceived as personal, specific, and financially insignificant*.

Xinxue Liu

• Served until 2023 on a scientific advisory board. This interest was perceived as personal, non-specific, and financially insignificant*.
• Serves on a DSMB. This interest was perceived as personal, non-specific, and financially insignificant*.
• Serves as  Investigator and lead statistician for Bill & Melinda Gates Foundation on TCV vaccine efficacy and effectiveness. This interest was perceived as non-personal, specific, and financially significant*.
• Served until 2023 as  Investigator and lead statistician for AstraZeneca on COVID-19 efficacy trial. This interest was perceived as non-personal, non-specific, and financially significant*.
• Serves as Investigator and lead statistician for NIHR and CEPI on COVID-19 policy trials. This interest was perceived as non-personal, nonspecific, and financially significant*.
• Serves as  Investigator and lead statistician for Serum Institute of India for Typhoid/Paratyphoid Bivalent vaccine CHIM study. This interest was perceived as non-personal, specific, and financially significant*.

* According to WHO's Guidelines for Declaration of Interests (WHO expert), an interest is considered "personal" if it generates financial or non-financial gain to the expert, such as consulting income or a patent. "Specificity" states whether the declared interest is a subject matter of the meeting or work to be undertaken. An interest has "financial significance" if the honoraria, consultancy fee or other received funding, including those received by expert's organization, from any single vaccine manufacturer or other vaccine-related company exceeds 5,000 USD in a calendar year. Likewise, a shareholding in any one vaccine manufacturer or other vaccine-related company in excess of 1,000 USD would also constitute a “significant shareholding”.