The typhoid vaccine story: from experimental medicine, epidemiology and field trials to policy.
Salmonella Typhi and Paratyphi A are the main causes of enteric fever, a very significant health concern in low and middle income countries today and a disease which had a major impact on the UK until the latter half of the 19th Century. It is spread through contaminated food and water and is best controlled by provision of clean water and use of adequate sanitation. Unfortunately, many low and middle income countries do not have the resources to solve the problem and vaccination has been considered a potential mitigation against the disease for more than 125 years. However, until recently no population level immunisation programmes have been recommended by WHO. Over the last decade a series of judicious studies using controlled human infection models and field trials have shown the potential of a new generation of protein-polysaccharide conjugate vaccines to control typhoid and reduce the huge global burden of disease. With policy recommendations in 2017 and a roll out starting in the pandemic, the impact is already being felt, but waning immunity is a real concern for sustained protection. Moreover, there are currently no licensed vaccines for paratyphoid, about one third of disease in South Asia, and the path forward for their development is not straightforward because standard licensure trials are considered not to be feasible. There are uncertainties about the control of enteric fever, but the first steps show great promise for improved health of children living in some of the most challenging circumstances.
