Epidemiological data show high disease incidence in young children and suggest that immunization programs should target children below two years of age: this is not possible with available vaccines. All vaccines were well tolerated. Compared to the polysaccharide vaccine, Vi-CRM induced a higher incidence of mild to moderate short lasting local pain. All Vi-CRM formulations induced higher Vi antibody levels compared to licensed control, with clear dose response relationship.
Vi-CRM did not elicit safety concerns, was highly immunogenic and is therefore suitable for further clinical testing in endemic populations of South Asia. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript.
AS and AP receive stock options from Novartis. Typhoid fever, a disease caused by Salmonella enterica serovar Typhi S. Typhi , represents a global public health issue causing over 21 million cases of disease and over , deaths per year worldwide [1]. Typhi related morbidity and mortality are reported [1] , [2]. Typhoid fever was previously considered a typical disease of school children and adolescents [3] ; however, most recent epidemiologic data from India, Pakistan, Bangladesh and Vietnam clearly show that younger children are also highly affected by typhoid fever and are at risk of severe disease [3] β [7].
These data have prompted a re-consideration of prevention strategies and suggest that immunization of subjects below two years could be a better approach to protect young children, to increase vaccination coverage and to reduce costs by concomitant delivery with routine vaccines of the Expanded Program on Immunization EPI [8] β [10]. Currently available typhoid vaccines, although moderately effective and well tolerated, cannot be administered to children younger than two years.
Additionally, the Vi polysaccharide induces a short lasting protection and requires repeated boosters which might cause hypo-responsiveness [11]. Since S. Typhi is an obligate human pathogen, an effective vaccination program could lead to substantial herd protection [12]. Therefore, new highly efficacious vaccines are needed to have the greatest public health impact in high risk areas and to allow their use in existing EPI vaccination programs.
