Reassessing potential economic value and health impact of effective Shigella vaccines

Abstract

The gram-negative bacterium Shigella is a leading cause of diarrheal morbidity and mortality in children in low- and middle-income countries. Several promising vaccine candidates are in late stages of clinical development against this increasingly antibiotic-resistant pathogen. However, considering the increasingly crowded and costly paediatric immunization schedule, and likely advent of other important new vaccines, it is unclear whether introduction of a Shigella vaccine would represent a high priority for international agencies or health ministries in low- and middle-income countries. To determine whether there is a compelling public health value proposition for a Shigella vaccine, we used the World Health Organization’s Full Value of Vaccine Assessment analytic framework and formulated five broad scientific, policy, economic and commercial-related propositions regarding the development of a Shigella vaccine. We also explored the current regulatory, clinical, policy and commercial challenges to a Shigella -containing combination vaccine development and adoption. Through a series of literature reviews, expert consultations, social science field studies and model-based analyses, we addressed each of these propositions. As described in a series of separate publications that are synthesized here, we concluded that the economic and public health value of a Shigella vaccine may be greater than previously recognized, particularly if it is found to also be effective against less severe forms of diarrheal disease and childhood stunting. The decision by pharmaceutical companies to develop a standalone vaccine or a multipathogen combination will be a key factor in determining its relative prioritization by various stakeholders in low- and middle-income countries.

The Full Value of Vaccine Assessments Concept—Current Opportunities and Recommendations

“…Moreover, while the paper by Hutubessy et al [9] provides a conceptual framework for conducting FVVAs and the recent paper by Trotter et al provides advice on its practical use [10], there is not yet concrete guidance on the optimal FVVA methods to be used, which would standardize the application of these assessments, facilitate fair comparisons, and allow larger themes or common evidence gaps to be identified. Building on the success of these prior applications and the FVVA framework [9,[17][18][19][20][21][22][23][24][25][26][27][28], we propose three recommendations to continue the development and standardization of FVVA methods, in order to maximize the usefulness of future FVVAs for country and global consumers.…”

“…Beyond the publication, there is also indication that maternal immunization is now also a priority for BMGF, who are engaged in supporting the development of further evidence to explore the capacity in low-resource settings for the potential future introduction of RSV and GBS. At the time of writing, the FVVA framework has been applied to a range of different diseases and vaccines, including Group B Streptococcus, tuberculosis, Group A Streptococcus, measles-rubella micro-array patches (MAPs), and Shigella [17][18][19][20][21][22][23][24][25][26][27][28] (Table 1). Many of these vaccines continue to advance in development, with donors such as Gavi and the Vaccine Alliance, discussing potential mechanisms to fund their introduction.…”

IgG Serum Antibodies to Shigella sonnei Lipopolysaccharide Are Inversely Associated with the Incidence of Culture-Proven S. sonnei Shigellosis in Israeli Children and Adolescents

“…Around 1.5–2 million cases of shigellosis also occur annually in high-income countries (HICs), mostly among toddlers in crowded communities, among travelers visiting less developed regions, soldiers who serve under field conditions in endemic regions, and among men who have sex with men [ 1 , 5 , 6 , 7 , 8 , 9 , 10 ]. Considering the global burden of shigellosis and the emerging antimicrobial resistance of Shigella [ 11 , 12 , 13 , 14 ], a Shigella vaccine is of high priority [ 15 , 16 , 17 , 18 , 19 ].…”