Acute Salmonellosis Research Articles

Persistent Salmonella infections in humans are associated with mutations in the BarA/SirA regulatory pathway

Several bacterial pathogens, including Salmonella enterica, can cause persistent infections in humans by mechanisms that are poorly understood. By comparing genomes of isolates longitudinally collected from 256 prolonged salmonellosis patients, we identified repeated mutations in global regulators, including the barA/sirA two-component regulatory system, across multiple patients and Salmonella serovars. Comparative RNA-seq analysis revealed that distinct mutations in barA/sirA led to diminished expression of Salmonella pathogenicity islands 1 and 4 genes, which are required for Salmonella invasion and enteritis. Moreover, barA/sirA mutants were attenuated in an acute salmonellosis mouse model and induced weaker transcription of host immune responses. In contrast, in a persistent infection mouse model, these mutants exhibited long-term colonization and prolonged shedding. Taken together, these findings suggest that selection of mutations in global virulence regulators facilitates persistent Salmonella infection in humans, by attenuating Salmonella virulence and inducing a weaker host inflammatory response.

Infection by Salmonella enterica Serovar Typhimurium DT104 Modulates Immune Responses, the Metabolome, and the Function of the Enteric Microbiota in Neonatal Broiler Chickens.

Salmonella enterica serovar Typhimurium incites salmonellosis in many different species including chickens and human beings. Acute salmonellosis was studied in neonatal broiler chicks by orally inoculating 2-day-old chicks with S. Typhimurium DT104. The temporal impact of disease (1, 2, and 4 days post-inoculation) on the structure and function of the enteric microbiota, on the bird's immune response in the ileum, cecum, and colon, and on the metabolome of digesta, breast muscle, liver, serum, and hippocampus were examined. Substantive histopathologic changes were observed in the small and large intestine, including the colon of chicks inoculated with S. Typhimurium, and increased in magnitude over the experimental time period. A variety of inflammatory genes (IFNγ, IL8, IL10, INOS, MIP1β, TGFβ2, TLR4, and TLR15) were temporally regulated. In addition, the metabolome of ileal digesta, breast muscle, liver, serum, and hippocampus was temporally altered in infected chicks. Although the structure of bacterial communities in digesta was not affected by S. Typhimurium infection, metabolomic analysis indicated that the function of the microbiota was changed. Collectively, the study findings demonstrate that infection of neonatal chicks by S. Typhimurium imparts a temporal and systemic impact on the host, affecting the immune system, the metabolome, and the function of the enteric microbiota.

Salmonella – still a threat? Epidemiological analysis of infecion

Salmonella infection causes morbidity and mortality throughout the world with the host immune response varying depending on whether the infection is acute and limited, or systemic and chronic. Global Salmonella infection, especially in developing countries, is a health and economic burden. These pathogen are responsible for millions of cases of food-borne illness each year, with substantial costs measured in hospitalizations and lost productivity. The growing number of bacteria resistant to the antibiotics commonly used to treat infections with this bacterium increases the use of alternative treatments. The species Lactobacillus and Bifidobacterium are the most commonly used probiotics to treat infectious diseases, including antibiotic diarrhea and traveler's diarrhea.It is a Gram-negative, non-spore-forming, rod-shaped and facultative anaerobic bacterium. However, they have the ability to survive inside infected cells. These bacteria cause various clinical forms of disease. The most dangerous sticks of typhoid fever (Salmonella typhi) and paradurium (Salmonella paratyphi) multiply only in the human body and cause a very serious infectious disease - typhoid fever. In turn, non-malignant salmonella, Salmonella bongori and countless serological varieties of Salmonella enterica colonize the digestive tract of many animal species and are pathogenic to humans, causing gastroenteritis, i.e. acute salmonellosis, sometimes classified as food poisoning. All Salmonella infections begin with ingestion with contaminated food or water.

Epidemiological and laboratory features of acute enteric infections

Background: This work describes etiological structure and statistics for causes of acute enteric infections and salmonellosis in modern conditions.
 Method: It was analyzed the common epidemiologic signs and indices of modern acute enteric infections (AEI), caused by opportunistic microorganisms (OMO), various viruses and salmonella.
 Result: The research also shows the integrative intoxication indicators of causal groups in endogenous intoxication which point to these phenomena being caused by autointoxication at the moment of one’s own cells disruption as well as induced by bacterial endo- and exotoxins.
 Conclusion: The work compares the etiology of AEI on the basis of reviewing their epidemiological attributes, changes in the integrative indication for endogenous intoxication, as well as vectors and causal correlations between hematological and microbiotic indicators.
 Bangladesh Journal of Medical Science Vol.20(4) 2021 p.748-755

A Study on Latent Equine Salmonellosis Based on Phenotypic and Molecular Methods in Kurdistan Province of Iran

BACKGROUND: Equine salmonellosis is an important infection with a wide variety of consequences including develop-ment of acute salmonellosis in the cases of predisposing factors, nosocomial infections, public health risk, and environmental contaminations. OBJECTIVES: The aim of this study was to evaluate the fecal shedders of Salmonella spp. in the horses of Kurdistan province of Iran using phenotypic and molecular approach. METHODS: A total of 130 fresh feces were randomly collected from horses in four age groups and both sexes in four seasons from all over Kurdistan province. The samples were analyzed for the isolation of Salmonella spp. with culture and biochemical method. An invA-based polymerase chain reaction (PCR) method was also carried out for detection of Salmo-nella spp. in pooled fecal samples, simultaneously. The isolates were further serotyped and the antimicrobial profile of the isolates was determined using Kirby-Bauer method. RESULTS: The results showed 1.53% (n=2) and 7.69% (n=10) by bacteriological methods and PCR method, respec-tively. There was no significant relation between the frequencies of Salmonella shedders and age, sex and season (p ≥0.05). The two isolates were recognized as Salmonella Typhimurium, showing 100% resistance against ampicillin, tetracycline, streptomycin, sulphamethoxazole, and chloramphenicol, and 50% resistance against gentamycin. CONCLUSIONS: Rapidity and accuracy of PCR versus phenotypic method makes it an appropriate procedure for the surveillance programs regarding Salmonella detection in feces. Approximately high prevalence of subclinical form in equine salmonellosis or Salmonella fecal carriers in the studied region is instigated to seriously apply strategies to manage and control the distribution of infection to susceptible hosts.

SpoT Induces Intracellular Salmonella Virulence Programs in the Phagosome.

Guanosine tetraphosphate (ppGpp) and guanosine pentaphosphate (pppGpp), together named (p)ppGpp, regulate diverse aspects of Salmonella pathogenesis, including synthesis of nutrients, resistance to inflammatory mediators, and expression of secretion systems. In Salmonella, these nucleotide alarmones are generated by the synthetase activities of RelA and SpoT proteins. In addition, the (p)ppGpp hydrolase activity of the bifunctional SpoT protein is essential to preserve cell viability. The contribution of SpoT to physiology and pathogenesis has proven elusive in organisms such as Salmonella, because the hydrolytic activity of this RelA and SpoT homologue (RSH) is vital to prevent inhibitory effects of (p)ppGpp produced by a functional RelA. Here, we describe the biochemical and functional characterization of a spoT-Δctd mutant Salmonella strain encoding a SpoT protein that lacks the C-terminal regulatory elements collectively referred to as "ctd." Salmonella expressing the spoT-Δctd variant hydrolyzes (p)ppGpp with similar kinetics to those of wild-type bacteria, but it is defective at synthesizing (p)ppGpp in response to acidic pH. Salmonella spoT-Δctd mutants have virtually normal adaptations to nutritional, nitrosative, and oxidative stresses, but poorly induce metal cation uptake systems and Salmonella pathogenicity island 2 (SPI-2) genes in response to the acidic pH of the phagosome. Importantly, spoT-Δctd mutant Salmonella replicates poorly intracellularly and is attenuated in a murine model of acute salmonellosis. Collectively, these investigations indicate that (p)ppGpp synthesized by SpoT serves a unique function in the adaptation of Salmonella to the intracellular environment of host phagocytes that cannot be compensated by the presence of a functional RelA.IMPORTANCE Pathogenic bacteria experience nutritional challenges during colonization and infection of mammalian hosts. Binding of the alarmone nucleotide guanosine tetraphosphate (ppGpp) to RNA polymerase coordinates metabolic adaptations and virulence gene transcription, increasing the fitness of diverse Gram-positive and Gram-negative bacteria as well as that of actinomycetes. Gammaproteobacteria such as Salmonella synthesize ppGpp by the combined activities of the closely related RelA and SpoT synthetases. Due to its profound inhibitory effects on growth, ppGpp must be removed; in Salmonella, this process is catalyzed by the vital hydrolytic activity of the bifunctional SpoT protein. Because SpoT hydrolase activity is essential in cells expressing a functional RelA, we have a very limited understanding of unique roles these two synthetases may assume during interactions of bacterial pathogens with their hosts. We describe here a SpoT truncation mutant that lacks ppGpp synthetase activity and all C-terminal regulatory domains but retains excellent hydrolase activity. Our studies of this mutant reveal that SpoT uniquely senses the acidification of phagosomes, inducing virulence programs that increase Salmonella fitness in an acute model of infection. Our investigations indicate that the coexistence of RelA/SpoT homologues in a bacterial cell is driven by the need to mount a stringent response to a myriad of physiological and host-specific signatures.

Cost of Salmonella Infections in Australia, 2015

Gastroenteritis caused from infections with Salmonella enterica (salmonellosis) causes significant morbidity in Australia. In addition to acute gastroenteritis, approximately 8.8% of people develop irritable bowel syndrome (IBS) and 8.5% of people develop reactive arthritis (ReA). We estimated the economic cost of salmonellosis and associated sequel illnesses in Australia in a typical year circa 2015. We estimated incidence, hospitalizations, other health care usage, absenteeism, and premature mortality for four age groups using a variety of complementary data sets. We calculated direct costs (health care) and indirect costs (lost productivity and premature mortality) by using Monte Carlo simulation to estimate 90% credible intervals (CrI) around our point estimates. We estimated that 90,833 cases, 4,312 hospitalizations, and 19 deaths occurred from salmonellosis in Australia circa 2015 at a direct cost of AUD 23.8 million (90% CrI, 19.3 to 28.9 million) and a total cost of AUD 124.4 million (90% CrI, 107.4 to 143.1 million). When IBS and ReA were included, the estimated direct cost was 35.7 million (90% CrI, 29.9 to 42.7 million) and the total cost was AUD 146.8 million (90% CrI, 127.8 to 167.9 million). Foodborne infections were responsible for AUD 88.9 million (90% CrI, 63.9 to 112.4 million) from acute salmonellosis and AUD 104.8 million (90% CrI, 75.5 to 132.3 million) when IBS and ReA were included. Targeted interventions to prevent illness could considerably reduce costs and societal impact from Salmonella infections and sequel illnesses in Australia.

Potential Involvement of Salmonella Infection in Autoimmunity.

In this work, we investigated the potential effects of nontyphoidal Salmonella infection on autoantibody (AA) formation. The titer and profiles of autoantibodies in the sera of patients with acute salmonellosis due to Salmonella enterica serovar Typhimurium (S. Typhimurium) or Salmonella enterica serovar Enteritidis (S. Enteritidis) infection, as well as in convalescent patients, were determined with indirect immunofluorescence. A significant increase of autoantibodies in acute diseases caused by both serotypes of Salmonella and during post infection by S. Enteritidis was detected. Antibody profile analysis by multivariate statistics revealed that this increase was non-specific and was not dependent on the infectious agent or disease stage. The results obtained suggest that nontyphoidal Salmonella infection contributes to the generation of autoantibodies and may play a role in autoimmune disease.

JAID/JSC Guidelines for Infection Treatment 2015-Intestinal infections.

JAID/JSC Guidelines for Infection Treatment 2015-Intestinal infections.

Economic impact of a Salmonella outbreak on a Welsh dairy farm and an estimation of the breakeven point for vaccination

Salmonellosis is a disease present in the cattle herds of England with clinical presentations such as abortion storms that can have devastating farm-level economic consequences. Using farm-specific costs and revenues,...

ГІСТОЛОГІЧНІ ЗМІНИ В ТЕЛЯТ ЗА ГОСТРОГО ПЕРЕБІГУ САЛЬМОНЕЛЬОЗУ

The results of study of histological changes in calves by age of 20 – 40 days at acute salmonellosis infection are presented. At a histological research the most expressed changes were registered in the liver, thin intestine and lymphoid organs that contingently reproduction here of the causative agent. At acute form of salmonellosis in calves of this age-grade characteristic histological changes include: submilliar, intralobular, coagulativ, areactive foci of necrosis in a liver; cell granuloma in a liver; the acute diffusive serous-catarrhal enteritis with a hemorrhagic accent; serous lymphadenitis of intestinal lymph nodes; the acute diffusive catarrhal abomasitis. Also nonspecific, but constant morphological signs of salmonellosis are hyperplasia Peyer’s patches of a small intestine, intestinal lymph nodes, spleen and dystrophic changes of parenchymal organs.An analysis and theoretical ground of pathogenetic mechanisms of the educed microstructural changes are conducted. It is shown that in pathogenesis of salmonellosis an important role is played bacteriaemia and toxinaemia, which result to the defeat of endothelia of vessels and blood cells with subsequent violation of mechanisms of haemostasis гand development of the infectiously-toxic shock.

A probiotic provides protection against acute salmonellosis in mice: Possible role of innate lymphid NKP46+ cells

A subset of innate lymphoid cells (ILCs), which produce IL-22 and function in protection against microbial infection, is generated via a local process in gut that is conditioned by commensal bacteria. We investigated the possibility that modulation of ILCs may contribute to the protective effect of certain bacteria in relation to pathogen infection. We fed BALB/c mice with L. rhamnosus JB-1 and characterized Peyer's patches NKp46+ cells. Additionally, the effect of feeding L. rhamnosus JB-1 on S. enterica serovar Typhimurium infection was determined. L. rhamnosus JB-1-feeding resulted in lower bacterial loads of Salmonella Typhimurium in the Peyer's patches, mesenteric lymph nodes and colon; and was associated with high levels of IL-22, RORγt, and CD127 expression by NKp46+ cells indicating an increase in ILC3s. Our findings indicate that Lactobacillus feeding regulates the innate lymphoid cell population that may contribute to host defensive function during Salmonella infection.

A case-control study to identify risk factors for acute salmonellosis in New Zealand dairy herds, 2011-2012.

In late 2011 the New Zealand Ministry for Primary Industries reported an increase in confirmed laboratory diagnoses of salmonellosis in dairy herds. To identify risk factors for herd-level outbreaks of salmonellosis we conducted a case-control study of New Zealand dairy herds in 2011-2012. In a multivariable analysis, use of continuous feed troughs [adjusted odds ratio (aOR) 6·2, 95% confidence interval (CI) 2·0-20], use of pelletized magnesium supplements (aOR 10, 95% CI 3·3-33) and use of palm kernel meal as a supplementary feed (aOR 8·7, 95% CI 2·5-30) were positively associated with a herd-level outbreak of salmonellosis between 1 July 2011 and 31 January 2012. We conclude that supplementary feeds used on dairy farms (regardless of type) need to be stored and handled appropriately to reduce the likelihood of bacterial contamination, particularly from birds and rodents. Magnesium supplementation in the pelletized form played a role in triggering outbreaks of acute salmonellosis in New Zealand dairy herds in 2011-2012.

Inflammatory Responses to Salmonella Infections Are Serotype-Specific.

The main purpose of this study was to investigate the profile of inflammatory response in patients with acute salmonellosis caused by two serotypes of Salmonella enterica, S. Enteritidis and S. Typhimurium, as well as in convalescent patients with previous acute disease caused by S. Enteritidis. Patients with acute disease showed significantly elevated levels of IL-1β, IL-17, IL-10, and calprotectin compared to healthy control subjects. In convalescent patients, these markers were also significantly elevated, with the exception of IL-1β. Multivariate statistical analyses with the use of these variables produced models with a good predictive accuracy resulting in excellent separation of the diseased and healthy cohorts studied. Overall, the results suggest that the profile of inflammatory response in this disease is determined, to a significant degree, by the serotype of Salmonella, and the profile of certain cytokines and calprotectin remains abnormal for a number of months following the acute disease stage.

A case definition for acute salmonellosis in dairy herds in New Zealand

This letter proposes a case definition for identifying and reporting cases of acute salmonellosis in dairy herds in New Zealand. We request veterinary practitioners in New Zealand use this case def...

Transient Hyperechoic Renal Cortex Caused by Dehydration and Induced Acute Renal Failure in Two Patients with Intra-Abdominal Infection

Increased renal cortical echogenicity can be seen in patients with various underlying renal abnormalities. However, there are no reports of hyperechoic cortex associated with volume depletion until now. Here, we describe two cases of hyperechoic cortex caused by severe dehydration due to liver abscess and acute salmonellosis which lead to nausea, vomiting, and diarrhea. After administering large amounts of fluid supplements, the renal functions dramatically recovered and the echogenicity of the renal cortex returned to normal. Redistribution of renal blood flow and cortical ischemia may play a role in changes in echogenicity that occur in the renal cortex. Additionally, studies on increased renal cortical echogenicity and dehydration are reviewed.

Resistance toSalmonellacarrier state: selection may be efficient but response depends on animal's age

Increasing resistance to acute salmonellosis (defined as bacteraemia in animals showing symptoms) is not sufficient for food safety, because of the risk of carrier state (when animals excrete bacteria without showing any symptoms). Increased resistance to Salmonella carrier state is therefore needed. Two experiments of divergent selection on resistance at a younger and a later age lead to significant differences between lines and allowed estimating genetic parameters on 4262 animals. Heritability of resistance was estimated at 0.16 in chicks, while it varied from 0.14 to 0.23 with analysed organ in adult hens. Genetic correlations between contamination of the different organs ranged from 0.46 to 0.67, while correlations between resistance at both ages were estimated at -0.50, showing that increasing genetic resistance of hens will reduce resistance in chicks. Highest estimated absolute values of genetic correlations between resistance and production traits were, for chicken contamination level, with number of eggs laid between 41 and 60 (0.37) and, for adult contamination, with number of eggs laid between 18 and 24 (0.37) or 25 and 40 (-0.33) weeks of age.

Pegylated Interferon Alfa-2b Plus Ribavirin in the Retreatment of Interferon-Ribavirin Nonresponder Patients

Inadequate data are available about retreatment of nonresponders to interferon (IFN) and ribavirin. Thus, this study evaluated the efficacy and tolerability of a 48-week therapy with pegylated IFN-alpha-2b plus high-dose ribavirin in patients who have failed to respond to the combination. Treatment up to 48 weeks also in patients who have failed to clear hepatitis C virus (HCV) RNA by week 24 was also evaluated. One hundred forty-one patients who previously did not respond to IFN and ribavirin, 86% with genotype 1 or 4 infection, 52% with high viral load (>800.000 IU/mL), 22% with cirrhosis, were retreated with pegylated IFN-alpha-2b 1.5 microg/kg per week and ribavirin 1000-1200 mg/day for 48 weeks and followed up for 24 weeks. By intent-to-treat analysis, 20% of patients achieved a sustained virologic response (SVR). SVR of genotype 1 patients was 19%. Independent predictors of SVR were low gamma-glutamyltransferase levels (OR, 22.9; 95% CI: 6.6-79.6) and low viral load (OR, 3.8; 95% CI: 1.1-12.6). Twelve (23%) out of 51 patients who were HCV RNA positive after 24 weeks of therapy achieved a late virologic response (after week 24) and 5 (10%) of them, all with genotype 1, achieved an SVR. Genotype was not associated with response (P = .2) or with early response (P = .3). Retreatment with pegylated IFN-alpha-2b and ribavirin of multi-experienced and "difficult to treat" nonresponder patients produced a very promising SVR. Accurate selection of patients, such as those with low viral load and low gamma-glutamyltransferase levels, and prolongation of therapy beyond 24 weeks also in HCV RNA-positive patients may further increase the rate of SVR.

Norfloxacin and Salmonella Excretion in Acute Gastroenteritis – a 6-Month Follow-up Study

In a controlled, randomized, double-blind study, 100 patients (66 women, 34 men; age 18-69 years) with acute salmonellosis were treated with norfloxacin (400 mg) or placebo tablets twice daily for 10 days to compare the effects on the excretion time of salmonella bacteria. In all patients salmonellae were detected in the stools before the start of treatment. The follow-up included 6 stool cultures after the start of treatment: day 3-4, day 12-14, and 4 times during 1-6 months. At 3-4 days there were 98% non-excretors in the norfloxacin group (46/47 patients) compared to 38% (17/45) in the placebo group (p < 0.001). The cumulative 6-month elimination rate in norfloxacin patients at 3-4 days was 72%, which was significantly (p = 0.0001) greater than the 31% in the placebo patients. However, there was no significant difference in the proportion of non-excretors or the elimination rate between the 2 groups at the following visits. Only one patient had an adverse event resulting in discontinuation of the treatment. We conclude that norfloxacin treatment for 10 days decreased the excretion of salmonella bacteria during the first week, but there was no difference in excretion rates 1-6 months after treatment initiation in the treatment versus placebo group.

Role of quinolones in the treatment of diarrhoeal diseases.

Diarrhoeal diseases are still an important health problem in both developing and developed countries, and resistance to commonly used antibiotics among enteric pathogens is a major issue. Quinolones have become important agents in the treatment of diarrhoeal diseases because of their excellent in vitro activity against pathogens and their pharmacological features. In many clinical studies, they appeared to be effective in the treatment of shigellosis and the prevention and treatment of diarrhoea in travellers. Several studies have demonstrated that single-dose therapy with these agents is sufficient in many cases. Their role in the treatment of acute salmonellosis is still controversial, because of their lack of efficacy in eliminating salmonella from the faeces.