Immunity and Protection Provided by Live Modified Vaccines Against Paratyphoid Salmonella in Poultry-An Applied Perspective.

Several serotypes of non-host-specific or paratyphoid Salmonella have been linked with contamination of poultry meat, and eggs, resulting in foodborne outbreaks in humans. Vaccination of poultry against paratyphoid Salmonella is a frequent strategy used to reduce the levels of infection and transmission, which ultimately can lead to lower rates of human infections. Live vaccines have been developed and used in poultry immediately after hatching as a result of their ability to colonize the gut, stimulate a mucosal immune response, induce a competitive inhibitory effect against homologous wild strains, and reduce colonization and excretion of Salmonella. Furthermore, vaccines can competitively exclude some heterologous strains of Salmonella from colonizing the gastrointestinal tract when young poultry are immunologically immature. In addition, various studies have suggested that booster vaccination with live vaccines a few weeks after initial vaccination is essential to increase the level of protection and achieve better cross-protective immunity. Vaccination of breeders, broilers, layers, and turkeys with modified live Salmonella vaccines is a common intervention that has become an important component in poultry companies' multistep prevention programs to meet increasingly demanding customer and regulatory food safety requirements. Both live and inactivated vaccines play a critical role in a comprehensive control program for chicken and turkey breeders and commercial layers. This review examines the response and protection conferred by live modified vaccines against non-host-specific Salmonella that can be considered for the design and implementation of vaccination strategies in poultry.

Artículo regular­Inmunidad y protección que brindan las vacunas vivas modificadas contra salmonelas paratíficas en la avicultura­Una perspectiva aplicada. Varios serotipos de Salmonella paratífica no específica de huésped se han relacionado con la contaminación de la carne de pollo y huevos lo que ha provocado brotes de origen alimentario en los seres humanos. La vacunación de aves comerciales contra Salmonella paratífica es una estrategia que se utiliza con frecuencia para reducir los niveles de infección y transmisión, que en última instancia puede conducir a tasas más bajas de infecciones en humanos. Se han desarrollado y utilizado vacunas vivas en aves comerciales inmediatamente después de la eclosión como resultado de su capacidad para colonizar el intestino, estimular una respuesta inmunitaria de la mucosa, inducir un efecto inhibidor competitivo contra cepas silvestres homólogas y reducir la colonización y excreción de Salmonella. Además, las vacunas pueden excluir competitivamente algunas cepas heterólogas de Salmonella de colonizar el tracto gastrointestinal cuando las aves jóvenes son inmunológicamente inmaduras. Además, varios estudios han sugerido que la vacunación de refuerzo con vacunas vivas unas semanas después de la vacunación inicial es esencial para aumentar el nivel de protección y lograr una mejor inmunidad de protección cruzada. La vacunación de reproductoras, pollos de engorde, aves de postura y pavos con vacunas vivas modificadas contra Salmonella es una intervención común que se ha convertido en un componente importante en los programas de prevención de múltiples pasos de las empresas avícolas para cumplir con los requisitos de los clientes y regulatorios de seguridad alimentaria. Tanto las vacunas vivas como las inactivadas desempeñan un papel fundamental en un programa de control integral para productores de pollos, pavos y aves ponedoras comerciales. Esta revisión examina la respuesta y la protección conferidas por las vacunas vivas modificadas contra Salmonella no específica del huésped que pueden ser consideradas para el diseño e implementación de estrategias de vacunación en la avicultura.

What's in a Name? Species-Wide Whole-Genome Sequencing Resolves Invasive and Noninvasive Lineages of Salmonella enterica Serotype Paratyphi B.

UNLABELLED: For 100 years, it has been obvious that Salmonella enterica strains sharing the serotype with the formula 1,4,[5],12:b:1,2-now known as Paratyphi B-can cause diseases ranging from serious systemic infections to self-limiting gastroenteritis. Despite considerable predicted diversity between strains carrying the common Paratyphi B serotype, there remain few methods that subdivide the group into groups that are congruent with their disease phenotypes. Paratyphi B therefore represents one of the canonical examples in Salmonella where serotyping combined with classical microbiological tests fails to provide clinically informative information. Here, we use genomics to provide the first high-resolution view of this serotype, placing it into a wider genomic context of the Salmonella enterica species. These analyses reveal why it has been impossible to subdivide this serotype based upon phenotypic and limited molecular approaches. By examining the genomic data in detail, we are able to identify common features that correlate with strains of clinical importance. The results presented here provide new diagnostic targets, as well as posing important new questions about the basis for the invasive disease phenotype observed in a subset of strains. IMPORTANCE: Salmonella enterica strains carrying the serotype Paratyphi B have long been known to possess Jekyll and Hyde characteristics; some cause gastroenteritis, while others cause serious invasive disease. Understanding what makes up the population of strains carrying this serotype, as well as the source of their invasive disease, is a 100-year-old puzzle that we address here using genomics. Our analysis provides the first high-resolution view of this serotype, placing strains carrying serotype Paratyphi B into the wider genomic context of the Salmonella enterica species. This work reveals a history of disease dating back to the middle ages, caused by a group of distinct lineages with various abilities to cause invasive disease. By quantifying the key genomic differences between the invasive and noninvasive populations, we are able to identify key virulence-related targets that can form the basis of simple, rapid, point-of-care tests.

Extended-spectrum ß-lactamase- and AmpC ß-lactamase-producing D-tartrate-positive Salmonella enterica serovar Paratyphi B from broilers and human patients in Belgium, 2008-10.

OBJECTIVES: To characterize the genetic determinants responsible for extended-spectrum cephalosporin (ESC) resistance of d-tartrate-positive Salmonella enterica subsp. enterica serovar Paratyphi B (serovar Paratyphi B dT+) strains that have emerged in poultry and humans in Belgium during 2008-10. METHODS: The ESC resistance genes among non-redundant serovar Paratyphi B dT+ strains were determined using PCR and sequencing. ESC phenotypes were horizontally transferred by conjugation. Extended-spectrum ß-lactamase (ESBL)- or AmpC-carrying plasmids were typed by PCR-based replicon typing, plasmid multilocus sequence typing and restriction fragment length polymorphism. The genetic relationship of ESC-resistant strains was assessed by XbaI PFGE and multilocus sequence typing. RESULTS: Since 2008, the proportion of serovar Paratyphi B dT+ strains from broiler origin has increased significantly to reach 36.5% in 2010. Among 95 non-duplicate serovar Paratyphi B dT+ strains, 35% were resistant to ESCs. At the same time, a few ESC-resistant serovar Paratyphi B dT+ strains from humans were also detected in Belgium. The most prevalent ESBL gene, blaCTX-M-1, and the AmpC cephalosporinase gene blaCMY-2 were identified on various conjugative IncI1 plasmids of different sequence types and with different additional non-ß-lactam phenotypes. Interestingly, the blaCTX-M-2 gene was located on large multireplicon IncHI2/P plasmids. In addition, highly ESC-resistant strains contained both the ESBL CTX-M-2 and the AmpC CMY-2 encoded by the IncHI2/P and IncI1 plasmids, respectively. All ESC-resistant serovar Paratyphi B dT+ strains belonged to sequence type 28 and showed the common PFGE pattern X8, as well as the chromosomal class 2 integron cassette array dfrA1-sat2-aadA1 previously described in the European poultry-associated serovar Paratyphi B dT+ clonal population. CONCLUSIONS: This study showed that the clonal population of multidrug-resistant serovar Paratyphi B dT+, persisting in broilers in Belgium for the last decade, recently acquired various plasmid-borne ESC resistance determinants, constituting a major concern for public health. Further surveillance programmes and research are an absolute necessity to understand their epidemiology and to propose interventions to limit the spread of ESC- and multidrug-resistant Salmonella spp.

O:2-CRM(197) conjugates against Salmonella Paratyphi A.

Enteric fevers remain a common and serious disease, affecting mainly children and adolescents in developing countries. Salmonella enterica serovar Typhi was believed to cause most enteric fever episodes, but several recent reports have shown an increasing incidence of S. Paratyphi A, encouraging the development of a bivalent vaccine to protect against both serovars, especially considering that at present there is no vaccine against S. Paratyphi A. The O-specific polysaccharide (O:2) of S. Paratyphi A is a protective antigen and clinical data have previously demonstrated the potential of using O:2 conjugate vaccines. Here we describe a new conjugation chemistry to link O:2 and the carrier protein CRM(197), using the terminus 3-deoxy-D-manno-octulosonic acid (KDO), thus leaving the O:2 chain unmodified. The new conjugates were tested in mice and compared with other O:2-antigen conjugates, synthesized adopting previously described methods that use CRM(197) as carrier protein. The newly developed conjugation chemistry yielded immunogenic conjugates with strong serum bactericidal activity against S. Paratyphi A.

Darkling beetles (Alphitobius diaperinus) and their larvae as potential vectors for the transfer of Campylobacter jejuni and Salmonella enterica serovar paratyphi B variant Java between successive broiler flocks.

Broiler flocks often become infected with Campylobacter and Salmonella, and the exact contamination routes are still not fully understood. Insects like darkling beetles and their larvae may play a role in transfer of the pathogens between consecutive cycles. In this study, several groups of beetles and their larvae were artificially contaminated with a mixture of Salmonella enterica serovar Paratyphi B Variant Java and three C. jejuni strains and kept for different time intervals before they were fed to individually housed chicks. Most inoculated insects were positive for Salmonella and Campylobacter just before they were fed to the chicks. However, Campylobacter could not be isolated from insects that were kept for 1 week before they were used to mimic an empty week between rearing cycles. All broilers fed insects that were inoculated with pathogens on the day of feeding showed colonization with Campylobacter and Salmonella at levels of 50 to 100%. Transfer of both pathogens by groups of insects that were kept for 1 week before feeding to the chicks was also observed, but at lower levels. Naturally contaminated insects that were collected at a commercial broiler farm colonized broilers at low levels as well. In conclusion, the fact that Salmonella and Campylobacter can be transmitted via beetles and their larvae to flocks in successive rearing cycles indicates that there should be intensive control programs for exclusion of these insects from broiler houses.

Novel attenuated Salmonella enterica serovar Choleraesuis strains as live vaccine candidates generated by signature-tagged mutagenesis.

Salmonella enterica serovar Choleraesuis is a host-adapted pathogen that causes swine paratyphoid. Signature-tagged mutagenesis (STM) was used to understand the pathogenicity of S. enterica serovar Choleraesuis in its natural host and also to develop novel attenuated live vaccine candidates against this disease. A library of 960 signature-tagged mutants of S. enterica serovar Choleraesuis was constructed and screened for attenuation in pigs. Thirty-three mutants were identified by the STM screening, and these mutants were further screened for attenuation by in vivo and in vitro competitive growth. Of these, 20 mutants targeting the outer membrane, type III secretion, transporter, lipopolysaccharide biosynthesis, and other unknown proteins were confirmed for attenuation. Five highly attenuated mutants (SC2D2 [ssaV], SC4A9 [gifsy-1], SC6F9 [dgoT], SC12B12 [ssaJ], and SC10B1[spiA]) were selected and evaluated for safety and protective efficacy in pigs by comparison with a commercially available vaccine strain. STM-attenuated live vaccine strains SC4A9 (gifsy-1) and SC2D2 (ssaV) were superior to commercially available live vaccine because they provided both safety and a protective immune response against challenge in pigs.

Multiple antimicrobial resistant Salmonella enterica serovar Paratyphi B variant Java in cattle: a case report.

An epidemiological investigation of a calf rearing premises and a closely associated dairy herd was carried out after the isolation of Salmonella enterica serovar Paratyphi B variant Java phage type 3b variant 2 from clinically diseased calves on the premises. The isolate was resistant to ampicillin, chloramphenicol, streptomycin, sulphonamides, tetracyclines, trimethoprim and cefoperazone. The organism was widespread on the calf unit and was also recovered from the dairy premises, mainly from groups of weaned calves. The investigation was extended to 10 epidemiologically linked farms but no S Java was isolated from any of the 40 to 60 samples collected from each premises. Molecular studies showed that the S Java isolates were genetically most similar to isolates from cases of human disease associated with ornamental fish tanks or feed. Long PCR and resistance gene profiling identified a resistance island which was indistinguishable from the human 'fish tank' strain of S Java and animal and human epidemic strains of S Typhimurium DT104. The isolates were clearly distinguished from multi-resistant S Java strains commonly associated with continental poultry. This is the first report of S Java with this resistance pattern in Great Britain.

Experimental and natural infection of early weaned pigs with Salmonella choleraesuis.

A model for experimental and natural infection of early weaned pigs with Salmonella choleraesuis, the aetiologic agent of swine paratyphoid, has been developed. An oral dose of 10(8) colony forming units (cfu) of S choleraesuis caused 100 per cent infection of 10 pigs inoculated, as indicated by recovery of the challenge organism from ileocolic lymph nodes collected at necropsy seven days post challenge. Seven of the pigs were observed shedding S choleraesuis at least once post S choleraesuis challenge. The cumulative incidence of shedding was 30 per cent and was sufficient to infect four of 10 pigs exposed naturally. Oral challenges with less than 10(8) cfu S choleraesuis were less effective in infecting early weaned pigs and did not result in natural transmission.

[Salmonella dublin on dairy farms in the North of the Netherlands]. / Salmonella dublin op melkveebedrijven in Noord-Nederland.

During the last century many calves and cows with Salmonella dublin infections are diagnosed in the North of the Netherlands, especially in the province of Friesland. In this paper are retrospectively traced the problems by paratyphoid infections in cattle, from 1919 till now, the diagnosis of which was made at the Animal Health Service in Friesland and North-Netherlands. Over the decennia a decrease is noticed for the percentage of necropsies of calves with S. dublin infections, although some irregular peaks appear. However since 1988 an increase is observed in dairy farms with S. dublin problems, revealing high mortality in calves, abortions and sick cows.

[Veterinary aspects of zoonose-related diseases in humans]. / Weterynaryjne aspekty odzwierzecych chorób czlowieka.

The paper presents the possibilities, difficulties and inabilities of veterinary medicine in the prophylaxis of zoonotic diseases in humans. With reference to this, the author characterized Salmonella paratyphi induced alimentary toxicon-infections, Q fever and chlamydiosis. The article also discusses current views on some neoplastic diseases in animals and their possible transmission to humans.

Distribution of paratyphoids on Saudi Arabian poultry farms and pathogenicity studies of predominant serotypes.

A total of 412 feed samples and 632 litter samples from 15 poultry farms (2 breeding farms and 13 rearing farms) were examined for salmonella. Twelve of these farms had salmonella in litter, five farms had salmonella in the feed and four had salmonella in both feed and litter. Seventeen feed samples (4.13%) and 121 litter samples (19.15%) were contaminated with salmonella. Sixteen salmonella serotypes were encountered, of which six were found in both feed and litter. Salmonella concord and S. livingstone were present in the litter of one breeding farm and its progeny farms. The five most frequently isolated salmonella serotypes in feed and litter were S. concord (17.39%), S. coeln (15.94%), S. livingstone (15.22%), S. manhattan (11.59%), and S. paratyphi B var. java (8.69%). The pathogenicities of those serotypes were determined by calculating their median lethal doses (LD50) 24 and 48 hr postinjection of 1,050 one-day-old broiler chicks via the navel into the yolk sac. The composite 48-hr LD50s (viable cells) were: S. concord, less than 8.8 X 10(3); S. livingstone, 1.1 X 10(5); S. manhattan, 3.5 X 10(5); S. coeln, 1.25 X 10(7); and S. paratyphi B var. java, 1.73 X 10(7).

[Tetracycline distribution in the body of animals and its effect on cellular interaction in the immune response]. / Raspredelenie tetraysiklinov v organizme zhivotnykh i vliianie ikh na vzaimodeistvie kletok v immunnom otvete

Distribution of tetracyclines and their effect on interaction of the cells in the immune response were studied on pigs and rabbits non-vaccinated, immunized with formolvaccin against paratyphoid fever and experimentally infected with the paratyphoid causative agent. It was found that oxytetracycline and tetracycline administered parentally to the animals formed complexes with the proteins and especially with albumins and gamma-globulins, were rapidly adsorbed by the lymphocytes and consumed by the cells of the reticulo-macro- and micro-phage systems, epithelium of the kidney cannaculi and the cells of the liver parenchyma. Immunomorphological changes accompanied by formation of antibodies to the antibiotics were found in the bloodforming-lymphoid system after repeated parental administrations of the tetracyclines. The titers of the antibodies to oxytetracycline and tetracycline were high by the 5th--14th day after the antibiotic administration and the relatively high levels persisted for 1.5 months. The use of tetracyclines during the induction stage of immunogenesis had a pronounced inhibitory effect on development of immunity against the paratyphoid fever antigen. On the basis of the tetracycline capacity for binding with immunoglobulins and intensive adsorption by the lymphocytes it is possible to suppose that the inhibitory effect of the antibiotics on immunogenesis was connected with their blocking the receptors of T- and B-lymphocytes.

Interaction of aflatoxin and paratyphoid infections in broiler chickens.

There was a significant (P less than 0.05) interaction resulting in increased mortality in chickens fed aflatoxin and infected with Salmonella worthington, S. thompson, S. derby, or S. typhimurium var. copenhagen which cause paratyphoid. There was no interaction on body weight or spleen weight; however, there wan an interaction with all four Salmonella species resulting in enlarged livers from which Salmonella could be isolated with increased frequency. Aflatoxin caused a decrease in total serum proteins but a dramatic increase in anti-Salmonella agglutinins in infected birds. These results suggest that aflatoxin impairs some component of the immune system other than that forming humoral antibodies and perhaps other than the reticuloendothelial system which have been reported previously to be impaired during aflatoxicosis in the chicken.

[Level of viral antibodies in normal and specific swine and bovine gamma globulin preparations]. / S'd'rzhanie na virusni antitela v "normalnite" i spetsifichnite svinski i govezhdi gamma-globulinovi preparati

Studied were 15 series of normal bovine gamma-globulin, 5 series of normal swine gamma-globulin, 7 series of Aujeszky gamma-globulin, 6 series of specific gamma-globulin against edema disease of pigs, 4 series of specific gamma-globulin against paratyphus, 5 series of Mixoglobulin-70, and one series of swine poly-globulin. All series of gamma-globulin preparations were studied for the presence of antibodies against Mixovirus parainfluenza-3 through the hemagglutinationinhibition reaction, antibodies against adenoviruses through the precipitation reaction in agar gel, and antibodies against the virus of Aujeszky's disease through the virus-neutralization reaction in tissue cultures.