New vaccine to combat typhoid

Prevalent in the 1940s and 1950s, typhoid shots gradually went out of reckoning in the next five decades, thanks to the availability of newer lines of medicines. But decades of treatment has made the bug Salmonella typhi resistant to many drugs. Indian researchers now show going back to the vaccine regime may not be a bad idea after all to protect kids against typhoid.

A water and food borne gastrointestinal infection, typhoid remains one of the major causes of illness and death in the developing world, killing an estimated 216,000 to 600,000 people annually.

Researchers from National Institute of Cholera and Enteric Diseases (NICED), Kolkata, Indian Council of Medical Research (ICMR), International Vaccine Institute (IVI), Seoul and University of West Ontario in Canada have found that a currently available yet underused vaccine against typhoid fever is highly effective in children. Interestingly, it also gives certain indirect protection to unvaccinated neighbours of vaccinated children.

The findings published in the latest issue of the New England Journal of Medicine may bolster the World Health Organisation’s push to start vaccine campaigns in poor countries against this often-fatal bacterial disease.

Known as Vi, the vaccine was 80 per cent effective in preventing typhoid fever among children aged two to five. Moreover, it offered 44 per cent protection for the unvaccinated kids who were in contact with the immunised children.

Typhoid once had a fatality of 10-20 per cent. But after a 1948 discovery that chloramphenicol drastically ameliorated enteric fevers and reduced the case fatality rate to less than one per cent, treatment of patients with oral chloramphenicol became the mainstay of typhoid control in developing countries for the next quarter century.

A rude awakening came in the 1970s, when epidemics of chloramphenicol-resistant typhoid occurred in Mexico and Vietnam.

Search for alternative therapies

These outbreaks stimulated a search for alternative oral antibiotic therapies and accelerated efforts to develop a new generation of vaccines. The efforts led to the development of two new vaccines Ty21a and Vi polysaccharide which were respectively licensed in the late 1980s and early 1990s.

But despite extensive data documenting the safety, efficacy, and practicality of the Vi and Ty21a vaccines, they have not been widely applied programmatically in developing countries.

In the late 1980s, multi-drug resistant strains of S. Typhi began to emerge. In 1999, WHO recommended typhoid vaccines may be used for immunisation of school-age children in areas where antibiotic-resistant typhoid was endemic.

Despite the WHO recommendation, use of Vi vaccine was limited, partly because of doubts about its ability to protect pre-school age children in the poorest settings and partly because of questions about Vi’s ability to confer “herd protection,” or protection of unvaccinated residents living in highly vaccinated areas.

To find out the answers, the researchers gave Vi injections to 37,673 slum-dwellers aged two years or older in the eastern suburbs of Kolkata. They all received a single dose of the vaccine between November 27 and December 31, 2004 and followed up for two years.

Results of Vi vaccine testing

Analysing the results, the team comprising former ICMR director general Nirmal Kumar Ganguly and his deputy Sujit Kumar Bhattacharaya found that overall, the vaccine was 61 per cent effective but the protection level went up to 80 per cent among kids who received routine immunisation.

The study also shows that kids who did not receive the shots but lived in the same clusters with vaccinated children had substantial protection against typhoid fever – a clear indication that the vaccine conferred substantial herd protection.

“This is important new information. The indirect protection of non-vaccinated persons by the Vi vaccine further bolsters the case for school-based immunisation to control endemic typhoid, since one might expect some indirect protection of preschool children as well,” said Myron M Levine from the centre for vaccine development in the University of Maryland.

“This vaccine is under the central government’s consideration. It is in the market, but the government has to take a decision whether programmes for the slums can be initiated,” Ganguly told Deccan Herald.

“The protection for children below five year is important because this age group was shown to be at high risk for typhoid in areas where the disease is endemic,” said John Clemens, IVI director general. The vaccine is also cheap (50 cent per dose).

In a separate IVI study conducted in five Asian countries, children in the same age group were found to have high rates of typhoid in Kolkata, Jakarta and Karachi confirming that the disease is not limited to school-aged children and adults.

The findings show preschool children could be targeted for mass campaigns.

Ganguly, however, conceded that typhoid fever does not pose a big health burden for India and is a problem only in areas with poor sanitation facilities. It can surely bring down the death levels in those pockets, he said.