ResearchPad - salmonella https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[A prospective study of bloodstream infections among febrile adolescents and adults attending Yangon General Hospital, Yangon, Myanmar]]> https://www.researchpad.co/article/elastic_article_13833 Bloodstream infection (BSI) is common among persons seeking healthcare for severe febrile illness in low-and middle-income countries. Data on community-onset BSI are few for some countries in Asia, including Myanmar. Such data are needed to inform empiric antimicrobial treatment of patients and to monitor and control antimicrobial resistance. We performed a one year, prospective study collecting information and blood cultures from patients presenting with fever at a tertiary referral hospital in Yangon, Myanmar. We found that almost 10% of participants had a bloodstream infection, and that Salmonella enterica serovars Typhi and Paratyphi A were the most common pathogens. Typhoidal Salmonella were universally resistant to ciprofloxacin. More than half of Escherichia coli and Klebsiella pneumoniae were resistant to extended-spectrum cephalosporins and resistance to carbapenems was also identified in some isolates. We show that typhoid and paratyphoid fever are common, and fluoroquinolone resistance is widespread. Extended-spectrum cephalosporin resistance is common in E. coli and K. pneumoniae and carbapenem resistance is present. Our findings inform empiric antimicrobial management of severe febrile illness, underscore the value of routine use of blood cultures, indicate that measures to prevent and control enteric fever are warranted, and suggest a need to monitor and mitigate antimicrobial resistance among community-acquired pathogens.

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<![CDATA[Towards understanding the antagonistic activity of phytic acid against common foodborne bacterial pathogens using a general linear model]]> https://www.researchpad.co/article/Nee28f4e6-a119-4233-a9a2-0c085b39343b

The increasing challenge of antibiotic resistance requires not only the discovery of new antibiotics, but also the development of new alternative approaches. Therefore, in the present study, we investigated for the first time the antibacterial potential of phytic acid (myo-inositol hexakisphosphate, IP6), a natural molecule that is ‘generally recognized as safe’ (FDA classification), against the proliferation of common foodborne bacterial pathogens such as Listeria monocytogenes, Staphylococcus aureus and Salmonella Typhimurium. Interestingly, compared to citric acid, IP6 was found to exhibit significantly greater inhibitory activity (P<0.05) against these pathogenic bacteria. The minimum inhibitory concentration of IP6 varied from 0.488 to 0.97 mg/ml for the Gram-positive bacteria that were tested, and was 0.244 mg/ml for the Gram-negative bacteria. Linear and general models were used to further explore the antibacterial effects of IP6. The developed models were validated using experimental growth data for L. monocytogenes, S. aureus and S. Typhimurium. Overall, the models were able to accurately predict the growth of L. monocytogenes, S. aureus, and S. Typhimuriumin Polymyxin acriflavine lithium chloride ceftazidime aesculin mannitol (PALCAM), Chapman broth, and xylose lysine xeoxycholate (XLD) broth, respectively. Remarkably, the early logarithmic growth phase of S. Typhimurium showed a rapid and severe decrease in a period of less than one hour, illustrating the bactericidal effect of IP6. These results suggest that IP6 is an efficient antibacterial agent and can be used to control the proliferation of foodborne pathogens. It has promising potential for environmentally friendly applications in the food industry, such as for food preservation, food safety, and for prolonging shelf life.

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<![CDATA[The Salmonella type III effector SpvC triggers the reverse transmigration of infected cells into the bloodstream]]> https://www.researchpad.co/article/N64786058-46f1-4e38-866e-6d07cb9ab4f4

Salmonella can appear in the bloodstream within CD18 expressing phagocytes following oral ingestion in as little as 15 minutes. Here, we provide evidence that the process underlying this phenomenon is reverse transmigration. Reverse transmigration is a normal host process in which dendritic cells can reenter the bloodstream by traversing endothelium in the basal to apical direction. We have developed an in vitro reverse transmigration assay in which dendritic cells are given the opportunity to cross endothelial monolayers in the basal to apical direction grown on membranes with small pores, modeling how such cells can penetrate the bloodstream. We demonstrate that exposing dendritic cells to microbial components negatively regulates reverse transmigration. We propose that microbial components normally cause the host to toggle between positively and negatively regulating reverse transmigration, balancing the need to resolve inflammation with inhibiting the spread of microbes. We show that Salmonella in part overcomes this negative regulation of reverse transmigration with the Salmonella pathogenicity island-2 encoded type III secretion system, which increases reverse transmigration by over an order of magnitude. The SPI-2 type III secretion system does this in part, but not entirely by injecting the type III effector SpvC into infected cells. We further demonstrate that SpvC greatly promotes early extra-intestinal dissemination in mice. This result combined with the previous observation that the spv operon is conserved amongst strains of non-typhoidal Salmonella capable of causing bacteremia in humans suggests that this pathway to the bloodstream could be important for understanding human infections.

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<![CDATA[Quantitative dynamics of Salmonella and E. coli in feces of feedlot cattle treated with ceftiofur and chlortetracycline]]> https://www.researchpad.co/article/Nd45d35d0-8623-4716-b387-5e4fac70c4ad

Antibiotic use in beef cattle is a risk factor for the expansion of antimicrobial-resistant Salmonella populations. However, actual changes in the quantity of Salmonella in cattle feces following antibiotic use have not been investigated. Previously, we observed an overall reduction in Salmonella prevalence in cattle feces associated with both ceftiofur crystalline-free acid (CCFA) and chlortetracycline (CTC) use; however, during the same time frame the prevalence of multidrug-resistant Salmonella increased. The purpose of this analysis was to quantify the dynamics of Salmonella using colony counting (via a spiral-plating method) and hydrolysis probe-based qPCR (TaqMan® qPCR). Additionally, we quantified antibiotic-resistant Salmonella by plating to agar containing antibiotics at Clinical & Laboratory Standards Institute breakpoint concentrations. Cattle were randomly assigned to 4 treatment groups across 16 pens in 2 replicates consisting of 88 cattle each. Fecal samples from Days 0, 4, 8, 14, 20, and 26 were subjected to quantification assays. Duplicate qPCR assays targeting the Salmonella invA gene were performed on total community DNA for 1,040 samples. Diluted fecal samples were spiral plated on plain Brilliant Green Agar (BGA) and BGA with ceftriaxone (4 μg/ml) or tetracycline (16 μg/ml). For comparison purposes, indicator non-type-specific (NTS) E. coli were also quantified by direct spiral plating. Quantity of NTS E. coli and Salmonella significantly decreased immediately following CCFA treatment. CTC treatment further decreased the quantity of Salmonella but not NTS E. coli. Effects of antibiotics on the imputed log10 quantity of Salmonella were analyzed via a multi-level mixed linear regression model. The invA gene copies decreased with CCFA treatment by approximately 2 log10 gene copies/g feces and remained low following additional CTC treatment. The quantities of tetracycline or ceftriaxone-resistant Salmonella were approximately 4 log10 CFU/g feces; however, most of the samples were under the quantification limit. The results of this study demonstrate that antibiotic use decreases the overall quantity of Salmonella in cattle feces in the short term; however, the overall quantities of antimicrobial-resistant NTS E. coli and Salmonella tend to remain at a constant level throughout.

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<![CDATA[FBXO7 sensitivity of phenotypic traits elucidated by a hypomorphic allele]]> https://www.researchpad.co/article/5c89776ad5eed0c4847d2c3f

FBXO7 encodes an F box containing protein that interacts with multiple partners to facilitate numerous cellular processes and has a canonical role as part of an SCF E3 ubiquitin ligase complex. Mutation of FBXO7 is responsible for an early onset Parkinsonian pyramidal syndrome and genome-wide association studies have linked variants in FBXO7 to erythroid traits. A putative orthologue in Drosophila, nutcracker, has been shown to regulate the proteasome, and deficiency of nutcracker results in male infertility. Therefore, we reasoned that modulating Fbxo7 levels in a murine model could provide insights into the role of this protein in mammals. We used a targeted gene trap model which retained 4–16% residual gene expression and assessed the sensitivity of phenotypic traits to gene dosage. Fbxo7 hypomorphs showed regenerative anaemia associated with a shorter erythrocyte half-life, and male mice were infertile. Alterations to T cell phenotypes were also observed, which intriguingly were both T cell intrinsic and extrinsic. Hypomorphic mice were also sensitive to infection with Salmonella, succumbing to a normally sublethal challenge. Despite these phenotypes, Fbxo7 hypomorphs were produced at a normal Mendelian ratio with a normal lifespan and no evidence of neurological symptoms. These data suggest that erythrocyte survival, T cell development and spermatogenesis are particularly sensitive to Fbxo7 gene dosage.

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<![CDATA[Contact with adult hen affects development of caecal microbiota in newly hatched chicks]]> https://www.researchpad.co/article/5c8977aad5eed0c4847d32a0

Chickens in commercial production are hatched in a clean hatchery environment in the absence of any contact with adult hens. However, Gallus gallus evolved to be hatched in a nest in contact with an adult hen which may act as a donor of gut microbiota. In this study, we therefore addressed the issue of microbiota development in newly hatched chickens with or without contact with an adult hen. We found that a mere 24-hour-long contact between a hen and newly hatched chickens was long enough for transfer of hen gut microbiota to chickens. Hens were efficient donors of Bacteroidetes and Actinobacteria. However, except for genus Faecalibacterium and bacterial species belonging to class Negativicutes, hens did not act as an important source of Gram-positive Firmicutes. Though common to the chicken intestinal tract, Lactobacilli and isolates from families Erysipelotrichaceae, Lachnospiraceae and Ruminococcaceae therefore originated from environmental sources instead of from the hens. These observation may have considerable consequences for the evidence-based design of the new generation of probiotics for poultry.

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<![CDATA[Salmonella-vectored vaccine delivering three Clostridium perfringens antigens protects poultry against necrotic enteritis]]> https://www.researchpad.co/article/5c6c75ddd5eed0c4843d0359

Necrotic enteritis is an economically important poultry disease caused by the bacterium Clostridium perfringens. There are currently no necrotic enteritis vaccines commercially available for use in broiler birds, the most important target population. Salmonella-vectored vaccines represent a convenient and effective option for controlling this disease. We used a single attenuated Salmonella vaccine strain, engineered to lyse within the host, to deliver up to three C. perfringens antigens. Two of the antigens were toxoids, based on C. perfringens α-toxin and NetB toxin. The third antigen was fructose-1,6-bisphosphate aldolase (Fba), a metabolic enzyme with an unknown role in virulence. Oral immunization with a single Salmonella vaccine strain producing either Fba, α-toxoid and NetB toxoid, or all three antigens, was immunogenic, inducing serum, cellular and mucosal responses against Salmonella and the vectored C. perfringens antigens. All three vaccine strains were partially protective against virulent C. perfringens challenge. The strains delivering Fba only or all three antigens provided the best protection. We also demonstrate that both toxins and Fba are present on the C. perfringens cell surface. The presence of Fba on the cell surface suggests that Fba may function as an adhesin.

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<![CDATA[MUC1 is a receptor for the Salmonella SiiE adhesin that enables apical invasion into enterocytes]]> https://www.researchpad.co/article/5c61e93fd5eed0c48496fa96

The cellular invasion machinery of the enteric pathogen Salmonella consists of a type III secretion system (T3SS) with injectable virulence factors that induce uptake by macropinocytosis. Salmonella invasion at the apical surface of intestinal epithelial cells is inefficient, presumably because of a glycosylated barrier formed by transmembrane mucins that prevents T3SS contact with host cells. We observed that Salmonella is capable of apical invasion of intestinal epithelial cells that express the transmembrane mucin MUC1. Knockout of MUC1 in HT29-MTX cells or removal of MUC1 sialic acids by neuraminidase treatment reduced Salmonella apical invasion but did not affect lateral invasion that is not hampered by a defensive barrier. A Salmonella deletion strain lacking the SiiE giant adhesin was unable to invade intestinal epithelial cells through MUC1. SiiE-positive Salmonella closely associated with the MUC1 layer at the apical surface, but invaded Salmonella were negative for the adhesin. Our findings uncover that the transmembrane mucin MUC1 is required for Salmonella SiiE-mediated entry of enterocytes via the apical route.

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<![CDATA[Role of SpaO in the assembly of the sorting platform of a Salmonella type III secretion system]]> https://www.researchpad.co/article/5c50c486d5eed0c4845e8885

Many bacterial pathogens and symbionts use type III secretion machines to interact with their hosts by injecting bacterial effector proteins into host target cells. A central component of this complex machine is the cytoplasmic sorting platform, which orchestrates the engagement and preparation of type III secreted proteins for their delivery to the needle complex, the substructure of the type III secretion system that mediates their passage through the bacterial envelope. The sorting platform is thought to be a dynamic structure whose components alternate between assembled and disassembled states. However, how this dynamic behavior is controlled is not understood. In S. Typhimurium a core component of the sorting platform is SpaO, which is synthesized in two tandemly translated products, a full length (SpaOL) and a short form (SpaOS) composed of the C-terminal 101 amino acids. Here we show that in the absence of SpaOS the assembly of the needle substructure of the needle complex, which requires a functional sorting platform, can still occur although with reduced efficiency. Consistent with this observation, in the absence of SpaOS secretion of effectors proteins, which requires a fully assembled injectisome, is only slightly compromised. In the absence of SpaOS we detect a significant number of fully assembled needle complexes that are not associated with fully assembled sorting platforms. We also find that although binding of SpaOL to SpaOS can be detected in the absence of other components of the sorting platform, this interaction is not detected in the context of a fully assembled sorting platform suggesting that SpaOS may not be a core structural component of the sorting platform. Consistent with this observation we find that SpaOS and OrgB, a component of the sorting platform, share the same binding surface on SpaOL. We conclude that SpaOS regulates the assembly of the sorting platform during type III secretion.

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<![CDATA[Contribution of the Cpx envelope stress system to metabolism and virulence regulation in Salmonella enterica serovar Typhimurium]]> https://www.researchpad.co/article/5c61e8cfd5eed0c48496f1be

The Cpx-envelope stress system regulates the expression of virulence factors in many Gram-negative pathogens. In Salmonella enterica serovar Typhimurium deletion of the sensor kinase CpxA but not of the response regulator CpxR results in the down regulation of the key regulator for invasion, HilA encoded by the Salmonella pathogenicity island 1 (SPI-1). Here, we provide evidence that cpxA deletion interferes with dephosphorylation of CpxR resulting in increased levels of active CpxR and consequently in misregulation of target genes. 14 potential operons were identified to be under direct control of CpxR. These include the virulence determinants ecotin, the omptin PgtE, and the SPI-2 regulator SsrB. The Tat-system and the PocR regulator that together promote anaerobic respiration of tetrathionate on 1,2-propanediol are also under direct CpxR control. Notably, 1,2-propanediol represses hilA expression. Thus, our work demonstrates for the first time the involvement of the Cpx system in a complex network mediating metabolism and virulence function.

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<![CDATA[Adding function to the genome of African Salmonella Typhimurium ST313 strain D23580]]> https://www.researchpad.co/article/5c478c3bd5eed0c484bd0f6c

Salmonella Typhimurium sequence type (ST) 313 causes invasive nontyphoidal Salmonella (iNTS) disease in sub-Saharan Africa, targeting susceptible HIV+, malarial, or malnourished individuals. An in-depth genomic comparison between the ST313 isolate D23580 and the well-characterized ST19 isolate 4/74 that causes gastroenteritis across the globe revealed extensive synteny. To understand how the 856 nucleotide variations generated phenotypic differences, we devised a large-scale experimental approach that involved the global gene expression analysis of strains D23580 and 4/74 grown in 16 infection-relevant growth conditions. Comparison of transcriptional patterns identified virulence and metabolic genes that were differentially expressed between D23580 versus 4/74, many of which were validated by proteomics. We also uncovered the S. Typhimurium D23580 and 4/74 genes that showed expression differences during infection of murine macrophages. Our comparative transcriptomic data are presented in a new enhanced version of the Salmonella expression compendium, SalComD23580: http://bioinf.gen.tcd.ie/cgi-bin/salcom_v2.pl. We discovered that the ablation of melibiose utilization was caused by three independent SNP mutations in D23580 that are shared across ST313 lineage 2, suggesting that the ability to catabolize this carbon source has been negatively selected during ST313 evolution. The data revealed a novel, to our knowledge, plasmid maintenance system involving a plasmid-encoded CysS cysteinyl-tRNA synthetase, highlighting the power of large-scale comparative multicondition analyses to pinpoint key phenotypic differences between bacterial pathovariants.

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<![CDATA[New Multidrug-Resistant Salmonella enterica Serovar Anatum Clone, Taiwan, 2015–2017]]> https://www.researchpad.co/article/5c354d32d5eed0c484dd4630

In 2011, a Salmonella enterica serovar Anatum clone emerged in Taiwan. During 2016–2017, infections increased dramatically, strongly associated with emergence and spread of multidrug-resistant strains with a plasmid carrying 11 resistance genes, including blaDHA-1. Because these resistant strains infect humans and food animals, control measures are urgently needed.

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<![CDATA[Antimicrobial resistance, plasmid, virulence, multilocus sequence typing and pulsed-field gel electrophoresis profiles of Salmonella enterica serovar Typhimurium clinical and environmental isolates from India]]> https://www.researchpad.co/article/5c1ab858d5eed0c484027ad1

Salmonella enterica serovar Typhimurium (S. Typhimurium) is a common serovar associated with non-typhoidal salmonellosis globally. However, there is insufficient data on molecular characterization of S. Typhimurium isolates from India. This study was undertaken to determine the antimicrobial resistance (AMR), plasmid, virulence profiles and molecular subtypes of S. Typhimurium Indian isolates (n = 70) of clinical and environmental origin isolated during 2010–2017. Antimicrobial susceptibility and minimum inhibitory concentrations were determined by disc diffusion and E-test methods respectively. Plasmid extraction was done following standard protocol. AMR genes, virulence genes and plasmid incompatibility types were detected by PCR; Pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST) were used for molecular subtyping. Majority (57%) of the study isolates was pan susceptible; five AMR profiles were observed among the resistant (43%) isolates. AMR was significantly (p = 0.004) associated with extra-intestinal isolates than intestinal isolates.The class 1 integron and plasmid-mediated quinolone resistance genes (qnrB1, qnrS1) in the resistant isolates were transferable by conjugation. Plasmids (≥1) ranging from 1.9 to 254kb size and of IncFIIS and/or FIB type were found in most isolates. A total of 39 pulsotypes by PFGE and four sequence types by MLST like ST36 (55.7%), ST19 (32.9%), ST313 (10%) and ST213 (1.4%) were observed. ST36 and ST19 were found circulating in both clinical and environmental host, while ST313 isolates had an exclusive clinical origin. All ST19 isolates (100%) were drug-resistant, while isolates belonging to ST313 (100%), ST213 (100%) and ST36 (82%) were pan susceptible. The virulence plasmid (VP) genes (spvB- spvC) were present in all genotypes except ST36. The VP was significantly (p<0.001) associated with extra-intestinal than intestinal isolates. Some environmental and clinical isolates were clonal indicating their zoonotic transmission. Knowledge on the molecular subtypes and AMR profiles of locally prevalent Salmonella serotypes is important for effective control of spread of resistant organisms. The MLST of S. Typhimurium isolates and its association with AMR, virulence profiles was not reported earlier from India.

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<![CDATA[Comparative genomics of transport proteins in seven Bacteroides species]]> https://www.researchpad.co/article/5c117bccd5eed0c48469a775

The communities of beneficial bacteria that live in our intestines, the gut microbiome, are important for the development and function of the immune system. Bacteroides species make up a significant fraction of the human gut microbiome, and can be probiotic and pathogenic, depending upon various genetic and environmental factors. These can cause disease conditions such as intra-abdominal sepsis, appendicitis, bacteremia, endocarditis, pericarditis, skin infections, brain abscesses and meningitis. In this study, we identify the transport systems and predict their substrates within seven Bacteroides species, all shown to be probiotic; however, four of them (B. thetaiotaomicron, B. vulgatus, B. ovatus, B. fragilis) can be pathogenic (probiotic and pathogenic; PAP), while B. cellulosilyticus, B. salanitronis and B. dorei are believed to play only probiotic roles (only probiotic; OP). The transport system characteristics of the four PAP and three OP strains were identified and tabulated, and results were compared among the seven strains, and with E. coli and Salmonella strains. The Bacteroides strains studied contain similarities and differences in the numbers and types of transport proteins tabulated, but both OP and PAP strains contain similar outer membrane carbohydrate receptors, pore-forming toxins and protein secretion systems, the similarities were noteworthy, but these Bacteroides strains showed striking differences with probiotic and pathogenic enteric bacteria, particularly with respect to their high affinity outer membrane receptors and auxiliary proteins involved in complex carbohydrate utilization. The results reveal striking similarities between the PAP and OP species of Bacteroides, and suggest that OP species may possess currently unrecognized pathogenic potential.

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<![CDATA[An improved DNA array-based classification method for the identification of Salmonella serotypes shows high concordance between traditional and genotypic testing]]> https://www.researchpad.co/article/5c1028fed5eed0c484248bb4

Previously we developed and tested the Salmonella GenoSerotyping Array (SGSA), which utilized oligonucleotide probes for O- and H- antigen biomarkers to perform accurate molecular serotyping of 57 Salmonella serotypes. Here we describe the development and validation of the ISO 17025 accredited second version of the SGSA (SGSA v. 2) with reliable and unambiguous molecular serotyping results for 112 serotypes of Salmonella which were verified both in silico and in vitro. Improvements included an expansion of the probe sets along with a new classifier tool for prediction of individual antigens and overall serotype from the array probe intensity results. The array classifier and probe sequences were validated in silico to high concordance using 36,153 draft genomes of diverse Salmonella serotypes assembled from public repositories. We obtained correct and unambiguous serotype assignments for 31,924 (88.30%) of the tested samples and a further 3,916 (10.83%) had fully concordant antigen predictions but could not be assigned to a single serotype. The SGSA v. 2 can directly use bacterial colonies with a limit of detection of 860 CFU/mL or purified DNA template at a concentration of 1.0 x 10−1 ng/μl. The SGSA v. 2 was also validated in the wet laboratory and certified using panel of 406 samples representing 185 different serotypes with correct antigen and serotype determinations for 60.89% of the panel and 18.31% correctly identified but an ambiguous overall serotype determination.

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<![CDATA[Modelling the cost-effectiveness of a rapid diagnostic test (IgMFA) for uncomplicated typhoid fever in Cambodia]]> https://www.researchpad.co/article/5bfc6254d5eed0c484ec8507

Typhoid fever is a common cause of fever in Cambodian children but diagnosis and treatment are usually presumptive owing to the lack of quick and accurate tests at an initial consultation. This study aimed to evaluate the cost-effectiveness of using a rapid diagnostic test (RDT) for typhoid fever diagnosis, an immunoglobulin M lateral flow assay (IgMFA), in a remote health centre setting in Cambodia from a healthcare provider perspective. A cost-effectiveness analysis (CEA) with decision analytic modelling was conducted. We constructed a decision tree model comparing the IgMFA versus clinical diagnosis in a hypothetical cohort with 1000 children in each arm. The costs included direct medical costs only. The eligibility was children (≤14 years old) with fever. Time horizon was day seven from the initial consultation. The number of treatment success in typhoid fever cases was the primary health outcome. The number of correctly diagnosed typhoid fever cases (true-positives) was the intermediate health outcome. We obtained the incremental cost effectiveness ratio (ICER), expressed as the difference in costs divided by the difference in the number of treatment success between the two arms. Sensitivity analyses were conducted. The IgMFA detected 5.87 more true-positives than the clinical diagnosis (38.45 versus 32.59) per 1000 children and there were 3.61 more treatment successes (46.78 versus 43.17). The incremental cost of the IgMFA was estimated at $5700; therefore, the ICER to have one additional treatment success was estimated to be $1579. The key drivers for the ICER were the relative sensitivity of IgMFA versus clinical diagnosis, the cost of IgMFA, and the prevalence of typhoid fever or multi-drug resistant strains. The IgMFA was more costly but more effective than the clinical diagnosis in the base-case analysis. An IgMFA could be more cost-effective than the base-case if the sensitivity of IgMFA was higher or cost lower. Decision makers may use a willingness-to-pay threshold that considers the additional cost of hospitalisation for treatment failures.

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<![CDATA[Salmonella escapes adaptive immune response via SIRT2 mediated modulation of innate immune response in dendritic cells]]> https://www.researchpad.co/article/5bfc623cd5eed0c484ec7908

Salmonella being a successful pathogen, employs a plethora of immune evasion mechanisms. This contributes to pathogenesis, persistence and also limits the efficacy of available treatment. All these contributing factors call upon for new drug targets against Salmonella. For the first time, we have demonstrated that Salmonella upregulates sirtuin 2 (SIRT2), an NAD+ dependent deacetylase in dendritic cells (DC). SIRT2 upregulation results in translocation of NFκB p65 to the nucleus. This further upregulates NOS2 transcription and nitric oxide (NO) production. NO subsequently shows antibacterial activity and suppresses T cell proliferation. NOS2 mediated effect of SIRT2 is further validated by the absence of effect of SIRT2 inhibition in NOS2-/- mice. Inhibition of SIRT2 increases intracellular survival of the pathogen and enhances antigen presentation in vitro. However, in vivo SIRT2 inhibition shows lower bacterial organ burden and reduced tissue damage. SIRT2 knockout mice also demonstrate reduced bacterial organ burden compared to wild-type mice. Collectively, our results prove the role of SIRT2 in Salmonella pathogenesis and the mechanism of action. This can aid in designing of host-targeted therapeutics directed towards inhibition of SIRT2.

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<![CDATA[Forecasting the incidence of salmonellosis in seniors in Canada: A trend analysis and the potential impact of the demographic shift]]> https://www.researchpad.co/article/5c06f038d5eed0c484c6d404

Salmonella infections remain an important public health issue in Canada and worldwide. Although the majority of Salmonella cases are self-limiting, some will lead to severe symptoms and occasionally severe invasive infections, especially in vulnerable populations such as seniors. This study was performed to assess temporal trends of Salmonella cases in seniors over 15 years (2014–2028) and assess possible impact of demographic shift on national incidence; taking into account of trends in other age groups. The numbers of reported Salmonella cases in seniors (60 years and over) in eight provinces and territories for a period of fifteen years were analysed (1998–2013) using a time-adjusted Poisson regression model. With the demographic changes predicted in the age-structure of the population and in the absence of any targeted interventions, our analysis showed the incidence of Salmonella cases in seniors could increase by 16% by 2028 and the multi-provincial incidence could increase by 5.3%. As a result, the age distribution amongst the Salmonella cases is expected to change with a higher proportion of cases in seniors and a smaller proportion in children (0–4 years old). Over the next decades, cases of infection, hospitalizations and deaths associated with Salmonella in seniors could represent a challenge to public health due to an aging population in Canada. As life expectancy increases in Canada, identification of unique risk factors and targeted prevention in seniors should be pursued to reduce the impact of the demographic shift on disease incidence.

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<![CDATA[CTX-M-65 Extended-Spectrum β-Lactamase–Producing Salmonella enterica Serotype Infantis, United States1]]> https://www.researchpad.co/article/5c1686b3d5eed0c48444466e

Extended-spectrum β-lactamases (ESBLs) confer resistance to clinically important third-generation cephalosporins, which are often used to treat invasive salmonellosis. In the United States, ESBLs are rarely found in Salmonella. However, in 2014, the US Food and Drug Administration found blaCTX-M-65 ESBL-producing Salmonella enterica serotype Infantis in retail chicken meat. The isolate had a rare pulsed-field gel electrophoresis pattern. To clarify the sources and potential effects on human health, we examined isolates with this pattern obtained from human surveillance and associated metadata. Using broth microdilution for antimicrobial susceptibility testing and whole-genome sequencing, we characterized the isolates. Of 34 isolates, 29 carried the blaCTX-M-65 gene with <9 additional resistance genes on 1 plasmid. Of 19 patients with travel information available, 12 (63%) reported recent travel to South America. Genetically, isolates from travelers, nontravelers, and retail chicken meat were similar. Expanded surveillance is needed to determine domestic sources and potentially prevent spread of this ESBL-containing plasmid.

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<![CDATA[In-Host Adaptation of Salmonella enterica Serotype Dublin during Prosthetic Hip Joint Infection]]> https://www.researchpad.co/article/5c1686c2d5eed0c4844448fa

Genome degradation has been central to the adaptation of Salmonella enterica serotypes to their hosts throughout evolution. We witnessed the patho-adaptation of a strain of Salmonella Dublin (a cattle-adapted serotype) to a human host during the course of a recurrent prosthetic hip joint infection evolving over several years.

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