Vi vaccine: Options for assessing effectiveness

Abstract

Vi polysaccharide vaccine against typhoid fever has several features that make it attractive for potential inclusion in routine immunization programs in developing countries. First, in contrast to earlier whole cell injectable vaccines, the parenteral Vi vaccine is associated with minimal side-effects. Second, Vi vaccine confers moderate protection against typhoid fever for at least three years following immunization. Third administration of Vi requires only a single dose. Fourth, Vi does not appear to require storage in a strict cold chain. Fifth, the technology for producing Vi appears potentially transferable to some developing countries. Despite these attractive features, deployment of Vi vaccine in routine immunization programs in developing countries has been hampered by several gaps in our knowledge about this vaccine. For example, although Vi has been demonstrated to be safe and immunogenic in children over 12 months age, no trial has evaluated the clinical protection of this vaccine when given in children under the age of five years. The performance of Vi vaccine at these early ages may be of particular importance to settings such as urban Delhi, where recent studies have demonstrated a considerable incidence of typhoid fever in children under three years of age. In addition, even for older children and adults it is not clear what the total preventive benefit of using Vi will be, since it is unknown to what extent mass immunization with Vi will confer herd immunity. Without such information, it is impossible to assess the likely cost-effectiveness of Vi vaccination, an issue of considerable importance to developing countries with limited per capita health care budgets. The evaluation of the effectiveness and cost-effectiveness of using Vi will require large-scale studies that directly measure the cost and clinical outcomes of vaccination. Two major options are available for these larger studies: 1) experimental evaluation of Vi vaccine in one or more target populations before introducing the vaccine into routine programs (“effectiveness trials”); and 2) introduction of Vi vaccine into immunization programs, followed by assessment of vaccine effectiveness by comparing health outcomes in persons who are vaccinated versus those who are not (“post-licensure studies”). While few would argue against the need for effectiveness trials before deciding to use Vi vaccine in a public health program requires careful consideration. This talk will describe the design and role of effectiveness trials in assisting public health decisions about the use of Vi vaccine.