Terms of Reference

The Working Group will be requested to review the scientific evidence and relevant programmatic considerations to formulate updated recommendations on the use of typhoid vaccines, with a focus on typhoid conjugate vaccines (TCVs). The proposed recommendations will be submitted for consideration by SAGE for revision of the global policy on typhoid vaccine use, and for subsequent updating of the WHO Position Paper on typhoid vaccines (2010). Publication of an updated position paper on typhoid vaccines is tentatively scheduled for 2018.

Specifically, the Working Group will review evidence on:

• the epidemiology and burden of disease caused by S. Typhi and implications for control, including risk factors, diagnostics and other issues related to typhoid surveillance and better understanding of the disease epidemiology;
• trends in antimicrobial resistance and implications for the control of typhoid fever;
• the safety, immunogenicity profile, effectiveness, duration of protection and indications for booster doses of TCVs in the context of existing typhoid vaccines;
• the optimum schedule and age of administration as well as delivery strategies for typhoid vaccines; including administration of TCVs to children under 2 years of age;
• the economic burden of typhoid fever and cost-effectiveness of vaccination (including vaccination in the context of other control strategies); and
• considerations for the use of typhoid vaccines in endemic as well as epidemic or emergency settings.

Composition

SAGE members

• Ilesh Jani (Chair of Working Group), Instituto Nacional de Saúde (National Institute for Health), Mozambique
• Kari Johansen, European Centre for Disease Prevention and Control, Sweden

Experts

• Narendra Arora, International Clinical Epidemiology Network, India
• Zulfiqar A. Bhutta (SickKids Center for Global Child Health, The Hospital for Sick Children, Canada; Center of Excellence in Women and Child Health, Aga Khan University, Pakistan)
• John A. Crump (Centre for International Health, University of Otago, New Zealand)
• Myron M. Levine (Department of Medicine; and Center for Vaccine Development, University of Maryland, USA)
• Dafrossa Lyimo (National EPI Manager (Dar es Salaam), Tanzania )
• Florian Marks (Department of Epidemiology, International Vaccine Institute, Republic of Korea)
• Mark A. Miller (Office of the Director; and Division of International Epidemiology and Population Studies, National Institutes of Health, USA)
• Christopher M. Parry (School of Tropical Medicine and Global Health, University of Nagasaki, Japan; and London School of Hygiene and Tropical Medicine, UK)
• Richard A. Strugnell (Department of Microbiology and Immunology, University of Melbourne, Australia)
• Dipika Sur (Consultant, Translational Health Science and Technology Institute, India)

WHO secretariat

• Focal point: Adwoa Bentsi-Enchill
• Joachim Hombach

Declaration of interests

All members completed a declaration of interests. The reported relevant interests are summarized below:

Zulfiqar A. Bhutta

• His institution (the Aga Khan University) received a grant from the former Novartis Vaccines Institute for Global Health (NVGH) to undertake a typhoid conjugate vaccine trial, for which he was Principal Investigator. This grant ceased in Sept 2012. This interest was assessed as non-personal, specific and financially significant.*
• His institution (The Hospital for Sick Children, Toronto) is recipient of a Bill and Melinda Gates Foundation (BMGF) grant for research on global trends in typhoid fever. This interest was assessed as non-personal, specific and financially significant.*

Myron M. Levine

• Has provided scientific advice, with no financial compensation, to a typhoid vaccine developer (Bharat Biotech) for the analysis and presentation of data on its licensed typhoid vaccine. This interest was assessed as non-personal, specific and financially insignificant.*
• His institution (the University of Maryland) has a license agreement with Bharat Biotech for a bivalent typhoid/paratyphoid vaccine (in early preclinical development) for which M Levine is a co-inventor. This interest was assessed as personal, specific and financially significant.*
• Through a Wellcome Trust grant to his institution (the University of Maryland), he is the Principal Investigator to develop and perform early clinical trials of a non-typhoidal Salmonella (NTS) conjugate vaccine for which he is a co-inventor. The University of Maryland has a technology transfer agreement with Bharat Biotech for this NTS vaccine candidate. This interest was assessed as personal, non-specific and financially significant.*
• His institution (the University of Maryland) has a license agreement with PaxVax to commercialize an oral cholera vaccine for which he is a co-inventor. Paxvax is also the current manufacturer of the live oral typhoid vaccine Ty21a. This interest was assessed as personal, non-specific and financially significant.*

Florian Marks

• His institution, the International Vaccine Institute (IVI), has a typhoid vaccine development program. IVI has technology transfer agreements and provides ongoing scientific and technical advice to three current developers of typhoid conjugate vaccines. F Marks is employed in the Epidemiology Department of IVI and this interest was assessed as non-personal, specific, and financially significant.*
• His institution (IVI) has received a research grant from the BMGF to conduct a multi-country typhoid burden study in Africa (the Severe Typhoid in Africa Program (SETA)), for which he is Principal Investigator. This interest was assessed as non-personal, specific and financially significant.*

Mark A. Miller

• His institution (the US National Institutes of Health) received a BMGF grant for the development of a biological reference standard for typhoid vaccines. This interest was assessed 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”.