(a) It is usually taken for granted that typhoid is a major public health problem in developing countries. However, careful analysis of data from current(1) and previous studies(2) shows that the absolute incidence of blood-culture proven typhoid episodes is only about 0.2% per year and, it contributes to a very small proportion of the total febrile episodes across all age groups (Table I). This is a very important observation because vaccination can/will protect only against typhoid episodes and not febrile episodes believed to be typhoid and/or loosely labelled ‘enteric fever’ and treated as typhoid.

(b) Increasing antibiotic resistance(3) is often cited to emphasize the public health significance of typhoid. However, the latest multi-centric international study reported resistance in India to be less than 10% to chloramphenicol, ampicillin, trimethoprim - sulphamethoxazole, combination of all three, and ciprofloxacin; and about 2% to ceftriaxone, but almost 60% to nalidixic acid(1). For unexplained reasons, bacterial resistance in India was much lower than other developing countries in the region; if true, this further reduces the public health significance of typhoid.

(c) The National immunization schedule included two doses of typhoid vaccine at school entry over two decades back; however this was not based on robust evidence and was abandoned. Changes in living conditions, hygiene practices, sanitation etc since then must also be factored-in if/when typhoid vaccination is considered in the present day.

(a) The main advantage of vaccine(s) with polysaccharide antigen(s) conjugated to proteins is the stimulation of T-cell dependent immune responses. The implication of this is that infants with relatively less mature immune systems would respond, which does not happen with polysaccharide alone. This would be a major benefit only if the disease (here typhoid) is a significant problem among young infants. This is often implied in literature by calculating the absolute number or relative proportion of typhoid cases among infants(1,2). However, it is more important to assess the importance of typhoid (and hence prevention) as an issue of public health significance rather than only as a clinical problem. Table 1 constructed from latest data(1) shows that typhoid is responsible not only for a very small proportion of febrile episodes in infants, but the proportion is less than in older children. Therefore, based on current information the conjugate vaccine has limited role in the Indian context, although this is the exact opposite of what is suggested(1). It should be noted that this conclusion need not be similar for other developing countries(4).

(b) The other purported advantage of typhoid conjugate vaccine is the belief that it confers superior protection as compared to the currently available vaccines. A recent Cochrane review(5) reported protective efficacy of 48% (95% CI=34-58%) at 2.5-3.0 years with three doses Ty21a vaccine; 55% (95% CI=30-70%) at 3.0 years with one dose Vi-polysaccharide vaccine and 87% (95% CI=56-96%) at 2.3 years with two doses Vi-rEPA (conjugate) vaccine, giving the impression that the conjugate vaccine is superior. However it is inappropriate to draw conclusions by comparing data between studies; the superiority of conjugate vaccine (if any) needs to be established through a randomized controlled comparative trial, rather than assumption by extrapolation.

(a) A Vi-rEPA conjugate vaccine prepared in USA was reported to have excellent protective efficacy in clinical trials conducted in Vietnam nearly a decade back(6). However, this vaccine also underwent clinical trials in China simultaneously; inexplicably the data is not available in the public domain. It is also surprising that no subsequent clinical trials have been reported with the vaccine.

(b) An Indian manufacturer has reportedly developed and tested a Vi-TT conjugate vaccine, but the trial design, outcome-measures, reporting format and conclusions are of questionable validity and more data is required to draw a definite conclusion.