Salmonella infections: an update on epidemiology, management, and prevention.

Salmonella species are a group of Gram-negative enterobacteria and known human pathogens in developing as well as industrialized countries. Despite significant advances in sanitation, provision of potable water, and highly controlled food chain surveillance, transmission of Salmonella spp. continues to affect communities, preferentially children, worldwide. This review summarizes updated concepts on typhoidal and non-typhoidal Salmonella infections, starting with a historical perspective that implicates typhoid Salmonella as a significant human pathogen since ancient times. We describe the epidemiology of this pathogen with emphasis on the most recent non-typhoidal Salmonella outbreaks in industrialized countries and continued outbreaks of typhoid Salmonella in underserved countries. An overview of clinical aspects of typhoid and non-typhoid infections in developing and industrialized countries, respectively, is provided, followed by a description on current treatment concepts and challenges treating multidrug-resistant Salmonella infections. We conclude with prevention recommendations, and recent research studies on vaccine prevention.

A new concept to stimulate mucosal as well as systemic immunity by parenteral vaccination as applied to the development of a live attenuated Salmonella enterica serovar Dublin vaccine.

A new concept of slow "drip feeding" that enables activation of mucosal as well as systemic immunity following parenteral vaccination was demonstrated using Salmonella Dublin in a mouse model. The live vaccine candidate, N-RM25, generated from a wild S. Dublin strain utilising metabolic-drift (spontaneous chromosomal) mutations had a unique sensitivity to bile and restricted growth in the presence of a very low concentration of bile salts No. 3 (0.075% (w/v)) but also had the ability to survive in a high concentration (19.2%) of the substance. Following intraperitoneal administration with 10(7) cfu, N-RM25 colonised and survived (10(1)-10(3) cfu/g) in the liver and spleen of mice for over 24 days without causing disease. A small number of the mutant organisms also penetrated the gall bladder and gut, most likely via the enterohepatic circulation. N-RM25 induced significant levels of serum IgG, IgA and intestinal secretory IgA. A second metabolic-drift mutant (R-NM29) that was rapidly eliminated from the liver and spleen and highly unlikely to penetrate the gall bladder and gut, stimulated some systemic immunity, but induced no mucosal immunity because it did not reach the immune stimulation sites within the gut. In vaccine trials, N-RM25 was significantly more effective in eliminating the homologous challenge bacteria (S. Dublin wild strain FD436) from the internal organs and intestinal lumen when compared to R-NM29 and the negative control. N-RM25 prevented the development of systemic infection and produced 100% protection.

Development of acquired immunity to Salmonella.

Salmonella enterica serovar Typhi (S. typhi) causes human typhoid fever, a serious and widespread disease in developing countries. Other Salmonella serovars are associated with food-borne infections. The recent emergence of multi-drug-resistant Salmonella strains highlights the need for better preventive measures, including vaccination. The available vaccines against Salmonella infection do not confer optimal protection. The design of new Salmonella vaccines must be based on the identification of suitable virulence genes and on knowledge of the immunological mechanisms of resistance to the disease. Control and clearance of a vaccine strain rely on the phagocyte oxidative burst, reactive nitrogen intermediates, inflammatory cytokines and CD4(+) TCR-alphabeta(+) T cells and are controlled by genes including NRAMP1 and MHC class II. Vaccine-induced resistance to reinfection requires the presence of Th1-type immunological memory and anti-Salmonella antibodies. The interaction between T and B cells is essential for the development of resistance following vaccination. The identification of immunodeficiencies that render individuals more susceptible to salmonellosis must be taken into consideration when designing and testing live attenuated Salmonella vaccines. An ideal live Salmonella vaccine should therefore be safe, regardless of the immunological status of the vaccinee, but still immunogenic.