Increasing rates of Salmonella Paratyphi A and the current status of its vaccine development

Abstract

Enteric fever caused by Salmonella enterica serovar Typhi and Salmonella enterica serovar Paratyphi is still a major disease burden mainly in developing countries. Previously, S. Typhi was believed to be the major cause of enteric fever. The real situation is now becoming clear with reports emerging from many Asian countries of S. Paratyphi, mostly S. Paratyphi A, causing a substantial number of cases of enteric fever. Although there have been advances in the use of the currently available typhoid vaccines and in the development of newer typhoid vaccines, paratyphoid vaccine development is lagging behind. Since the disease caused by S. Typhi and S. Paratyphi are clinically indistinguishable and are commonly termed ‘enteric’ fever, it will be necessary to have a vaccine available against both S. Typhi and S. Paratyphi A as a bivalent ‘enteric fever vaccine’.

Keywords::

• conjugate vaccine
• enteric fever
• live attenuated vaccine
• Salmonella Paratyphi A
• Salmonella Typhi
• Ty21a
• Vi polysaccharide vaccine

Financial & competing interests disclosure

All the authors are working with the International Vaccine Institute which works in the field of typhoid and paratyphoid vaccine development and have received grants to develop new generation typhoid vaccine. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • The organisms responsible for the enteric fever are Salmonella enterica serovar Typhi (S. Typhi) and Salmonella enterica serovar Paratyphi (S. Paratyphi) A, B and C.

• • In the past, S. Typhi was considered the predominant cause of enteric fever, however, recent data from various parts of Asia suggest the increasing proportion of S. Paratyphi, particularly S. Paratyphi A.

• • High percentage of S. Paratyphi A isolates are resistant to nalidixic acid, which is a marker for reduced fluoroquinolone treatment outcome.

• • S. Paratyphi A causes a very similar disease as S. Typhi and it is difficult to differentiate between the two clinically; only laboratory tests can diagnose the exact cause of fever, adding another challenge as these tests have low sensitivity.

• • The old killed whole-cell parenteral TAB vaccine was a trivalent combination of inactivated S. Typhi, S. Paratyphi A and S. Paratyphi B, but due to its high reactogenicity, it is no longer licensed.

• • Currently available typhoid vaccines (Vi polysaccharide and Ty21a) are indicated for S. Typhi only.

• • The Ty21a oral typhoid vaccine may provide some protection against S. Paratyphi B.

• • Several live attenuated oral vaccine candidates against S. Paratyphi A are at the preclinical and early clinical stages of development.

• • Conjugate vaccine based on the O-specific polysaccharide (OSP) of S. Paratyphi A bound to tetanus toxoid (TT) was evaluated in Phase I and II clinical trials in Vietnam and China. The vaccine was found to be safe and immunogenic.

• • The scientific data and the experience with the Vi polysaccharide vaccine indicate that future enteric fever prevention strategies in Asia must focus on S. Paratyphi A in addition to S. Typhi and underscores the importance of developing bivalent vaccines to prevent enteric fever as a whole.