Response to: Szu SC. Development of Vi conjugate – a new generation of typhoid vaccine. Expert Rev. Vaccines 12(11), 1273–1286 (2013).
The current developments with the production and utility of new generation conjugated typhoid vaccines have been meticulously reviewed by Szu Citation[1]. Nevertheless, the efficacy of different vaccines conjugated to different carrier proteins like rEPA, diphtheria or tetanus toxoid, recombinant diphtheria toxin (CRM197), might be far from ideal during infection of vaccine recipients by Vi-negative Salmonella typhi strains.
The existence of naturally occurring Vi-negative strains has been well established now during molecular studies though Vi-negative isolates would not be agglutinated by anti-Vi sera have been known for several decades. During the 1960s, they were identified during phage typing in various geographical locations globally Citation[2].
Genetic control of Vi-expression has been determined, and it is possible to confirm Vi-negative S. typhi. The synthesis and transportation proteins of the Vi capsular polysaccharide of Salmonella enterica serovar Typhi (serovar Typhi) are encoded by the viaB operon, which resides on a 134-kb pathogenicity island known as SPI-7. During analysis of 60 stored strains of serovar Typhi from the Faisalabad region of Pakistan by PCR for the presence of SPI-7 and two genes essential for Vi production: tviA and tviB, 9 (15%) were tested negative for both tviA and tviB, while only two of such strains lacked SPI-7 Citation[3]. Furthermore, the 42 multiplex PCR-positive isolates from the Faisalabad region of Pakistan included 9 Vi negatives Citation[4].
The expanded usage of conjugated Vi vaccines Citation[1] in areas with frequent circulation of Vi-negative isolates Citation[3,4] could aid in selection and dissemination of the Vi-negative strains in the community. The role of circulating Vi-negative strains could be tremendous following extended usage of Vi vaccines. After mass vaccinations, they could be selected with extensive dissemination and disease morbidity and mortality. Such events could be avoided by the use of live attenuated vaccines.
The clinical picture associated with such Vi-negative isolates would be indistinguishable from the one caused by isolates carrying Vi antigen Citation[5]. The role of circulating Vi-negative isolates in the community for failures associated with Vi vaccines has not been examined. The reported failures encountered during different randomized trials with typhoid fever vaccines Citation[6] might well have been associated with circulating Vi-negative strains.
Financial & competing interests disclosure
The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
References
- Szu SC. Development of Vi conjugate - a new generation of typhoid vaccine. Expert Rev Vaccines 2013;12(11):1273-86
- International Committee for Enteric Phage typing. The geographical distribution of Salmonella typhi and Salmonella paratyphi A and B during the period 1 January 1969-31 December 1969. J Hyg Camb 1973;71:59-84
- Baker S, Sarwar Y, Aziz H, et al. Detection of Vi-negative Salmonella enterica serovar typhi in the peripheral blood of patients with typhoid fever in the Faisalabad region of Pakistan. J Clin Microbiol 2005;43(9):4418-25
- Ali A, Haque A, Haque A, et al. Multiplex PCR for differential diagnosis of emerging typhoidal pathogens directly from blood samples. Epidemiol Infect 2009;137:102-7
- Hornick RB, Greisman SE, Woodward TE, et al. Typhoid fever: pathogenesis and immunological control (second of two parts). N Engl J Med 1970;283:686-91
- Fraser A, Paul M, Goldberg E, et al. Typhoid fever vaccines: systematic review and meta-analysis of randomized controlled trials. Vaccine 2007;25:7848-57