Typhoid Conjugate Vaccines and Enteric Fever Control: Where to Next?

After the unprecedented success and acceleration of the global agenda towards typhoid fever control with a strong World Health Organization recommendation and the approval of funding from Gavi, the Vaccine Alliance (Gavi), for the use of a new typhoid conjugate vaccine (TCV), we should turn our minds to the challenges that remain ahead. Despite the evidence showing the safety and clinical efficacy of TCV in endemic populations in developing countries, we should remain vigilant and explore hurdles for the full public health impact of TCV, including vaccine supply for the potential global demand, immunization strategies to optimize the effectiveness and long-term protection provided by the vaccines, potential use of TCV in outbreak settings, and scenarios for addressing chronic carriers. Finally, challenges face endemic countries with poor surveillance systems concerning awareness of the need for TCV and the extent of the issue across their populations, and how to target immunization strategies appropriately.

Toward Control? The Prospects and Challenges of Typhoid Conjugate Vaccine Introduction.

With a newly World Health Organization (WHO)-prequalified typhoid conjugate vaccine (TCV), Gavi funding for eligible countries, and a WHO policy recommendation for TCV use, now is the time for countries to introduce TCVs as part of an integrated typhoid control program, particularly in light of the increasing burden of antimicrobial resistance. Continued vaccine development efforts will lead to secure supply of low-cost vaccines, and ongoing vaccine studies will provide critical vaccine performance data and inform optimal deployment strategies, in both routine use and in outbreak settings. TCV programs should include thoughtful communication planning and community engagement to counter vaccine hesitancy.

A Global Agenda for Typhoid Control-A Perspective from the Bill & Melinda Gates Foundation.

Recognizing that enteric fever disproportionately affects the poorest and the most vulnerable communities that have limited access to improved sanitation, safe water sources, and optimal medical care, the Bill & Melinda Gates Foundation has funded efforts to augment global understanding of the disease since the foundation's inception. At the turn of the century, early efforts focused on characterizing the burden of disease in Asia and evaluating use of the available Vi-polysaccharide vaccines through the Diseases of the Most Impoverished projects at the International Vaccine Institute (IVI). More recent efforts have centered on supporting development of typhoid conjugate vaccines and expanding disease surveillance efforts into Africa, as well as generating a greater understanding of the clinical severity and sequelae of enteric fever in Africa, Asia, and India. The Typhoid Vaccine Accelerator Consortium is playing a critical role in coordinating these and other global efforts for the control of typhoid fever. Here, we outline the scope of support and strategic view of the foundation and describe how, by working through strong partnerships, we can realize a radical reduction of the significance of enteric fever as a global public health problem in the next 10 to 15 years.

Challenges and Opportunities for Typhoid Fever Control: A Call for Coordinated Action.

The burden of enteric fever caused by Salmonella enterica serovars Typhi and Paratyphi is substantial and has high impact in toddlers and young children. This burden is relatively well documented in Asia, and this supplement provides new data on the substantial burden in several sub-Saharan African countries. Challenges in standardized surveillance and imperfect diagnostic tools have resulted in patchy local disease data, which are not well acknowledged or integrated into local country evidence and health awareness for decision making. There is a need to strengthen diagnostics for the generation of burden data in country. Furthermore, the guidelines and training for treatment of enteric fever cases in Africa are sorely needed to help mitigate the inappropriate use of antimicrobial treatment. Classic water safety and access to sanitation development remain powerful tools for the control of typhoid fever, yet the huge economic costs and long timelines are unlikely to provide a short- to middle-term solution. Emerging threats, including multidrug resistance and increasing urbanization in regions such as sub-Saharan Africa, warrant focused attention to shorter-term interventions including immunization, and must include vaccine strategies with the new typhoid conjugate vaccines.

Consensus statement understanding health and malnutrition through a systems approach: the ENOUGH program for early life.

Nutrition research, like most biomedical disciplines, adopted and often uses experimental approaches based on Beadle and Tatum's one gene-one polypeptide hypothesis, thereby reducing biological processes to single reactions or pathways. Systems thinking is needed to understand the complexity of health and disease processes requiring measurements of physiological processes, as well as environmental and social factors, which may alter the expression of genetic information. Analysis of physiological processes with omics technologies to assess systems' responses has only become available over the past decade and remains costly. Studies of environmental and social conditions known to alter health are often not connected to biomedical research. While these facts are widely accepted, developing and conducting comprehensive research programs for health are often beyond financial and human resources of single research groups. We propose a new research program on essential nutrients for optimal underpinning of growth and health (ENOUGH) that will use systems approaches with more comprehensive measurements and biostatistical analysis of the many biological and environmental factors that influence undernutrition. Creating a knowledge base for nutrition and health is a necessary first step toward developing solutions targeted to different populations in diverse social and physical environments for the two billion undernourished people in developed and developing economies.

Building global advocacy for nutrition: a review of the European and U.S. landscapes.

BACKGROUND: An estimated two billion people globally suffer from undernutrition, and yet, despite consensus that improving nutrition is one of the best investments for promoting health and alleviating poverty, nutrition remains chronically underfunded and under-prioritized. Successfully scaling global efforts to address undernutrition requires an understanding of the landscape of potential donors and partners that can be mobilized toward improving nutrition globally. OBJECTIVE: To conduct independent reviews of the European and US landscapes of donors and partners focused on undernutrition, and identify opportunities to leverage outreach and advocacy efforts toward increased engagement and funding for nutrition. METHODS: We present the primary findings from two independent landscaping studies conducted between September 2010 and March 2011. Research methods included desk-based research and interviews with stakeholders in bilateral and multilateral organizations (n=19), private industries (n=46), private funders (n=16), and civil society organizations (n=29). We report the key thematic findings by sector and the challenges and opportunities for increased engagement and funding for nutrition. RESULTS: Nutrition is a growing priority for a number of stakeholders across sectors. Strategic commitment to nutrition is emerging across multilateral and bilateral donor agencies; the private sector is increasingly interested in engaging in addressing undernutrition; and nongovernmental and civil society groups are engaged in nutrition advocacy. Key opportunities to increase funding and partnership across sectors include leveraging bilateral and multilateral investments for nutrition across development priorities while ensuring sound commitments within donor policies, focusing on engaging the private sector across the food value chain, mobilizing new resources from private funders through effective communication and outreach, and continuing to prioritize ongoing impact assessment across a range of interventions. CONCLUSIONS: Understanding the current European and US landscape of nutrition stakeholders helps to inform efforts to scale the type of investments and partnership needed to make effective impacts on undernutrition globally. Turning the existing opportunities into results will require effective coordination, strong communication, and active participation across sectors.