Typhoid

Typhoid is caused by an infection with Salmonella enterica subspecies enterica serovar Typhi (S. Typhi).

Typhoid fever presents as a non-specific, febrile, systemic illness with a wide variety of general symptoms – such as malaise, headache, abdominal pain, chills, anorexia, diarrhoea, weight loss and constipation – and may result in severe and sometimes fatal complications.

The disease causes considerable illness and death in developing countries. Although the true incidence of typhoid fever is not known, it is estimated that there are 26 million cases each year, causing 216 000 deaths.

In endemic areas, typhoid affects infants, school-age children and young adults in particular. In developed countries it is a minor public health threat, but people can contract it after visiting endemic areas.

Vaccination

Vaccination prevents typhoid. S. typhi expresses a capsule made of polysaccharides, which was discovered in 1934 and named Vi – short for virulence. It is still considered the main virulence factor and only recently it has been shown that the Vi capsule protects S. Typhi from attack by the human immune system. Vi is considered a protective antigen.

Licensed typhoid vaccines, the oral live attenuated Ty21a vaccine and the injectable Vi polysaccharide vaccine are available in the UK. These vaccines are not suitable for children under 5 and 2 years of age respectively. Novel Vi conjugate vaccines are being developed, and these are highly immunogenic, safe and effective in infants and pre-school age children.

Standardisation

At NIBSC, 2 World Health Organisation (WHO) International Standards (IS) for whole cell typhoid vaccines are in stock. Two ISs for Salmonella species that cause disease in poultry are also available.  NIBSC staff drafted WHO guidelines on the quality, safety and efficacy of typhoid conjugate vaccines: part A guidelines on manufacture and control.

Control

The enteric vaccine group is responsible for the batch release of plain Vi polysaccharide vaccine for the EU. This involves reviewing batch manufacturing records to make sure the batch meets the specification of the vaccine product licence. As well as this, we submit each batch to:

• visual inspection
• an immunoassay to determine the amount of Vi polysaccharide
• a test for the presence of endotoxins
• analysis by nuclear magnetic resonance spectroscopy to establish the level of O-acetylation of Vi polysaccharide – critical for the induction protective antibodies

Research and development 

Currently, there is great interest in promoting the use of new Vi conjugate vaccines for children and infants. With the help of our colleagues at NIBSC and from WHO and the Bill and Melinda Gates Foundation, we carry out a range of tasks to support this programme.

One important aspect is to improve standardisation of assays for analysis of antibodies to Vi polysaccharide. Our R&D projects are aligned to this objective, and they involve designing proficiency studies and developing: 

• a capture ELISA to measure antibodies that react with Vi polysaccharide and to quantify Vi in vaccines 
• an immunoassay using a chemically modified Vi polysaccharide with improved binding capabilities to measure antibodies that react with Vi polysaccharide