Autologous hematopoietic stem cell product contaminated with Salmonella due to occult salmonellosis in an asymptomatic donor.

Recent advancements in infectious disease testing methods and pathogen reduction technologies have greatly reduced the incidence of microbial contamination of allogeneic blood products. Despite this significant reduction, contamination of autologous cellular therapy products remains a challenging issue, as many of these mitigation strategies are not feasible for such products. Most microorganisms isolated from cellular therapy products are Gram-positive normal skin flora, and studies have demonstrated that adverse effects are infrequent when these contaminated products are infused. However, no prior report has documented an autologous hematopoietic stem cell (HSC) or other cellular therapy product contaminated with Salmonella bacteria-a pathogenic Gram-negative organism. We present the first known case of Salmonella contaminating an HSC product secondary to occult salmonellosis in the donor, and discuss the implications of this contaminating organism and the therapeutic dilemma posed by this scenario.

A systemic review of literatures on human Salmonella enterica serovars in Nigeria (1999-2018).

INTRODUCTION: Salmonella infections are endemic in Nigeria. There is lack of reliable data on culture-positive Salmonella with national coverage. This systemic review of literatures was undertaken to aggregate data on culture proven cases of human Salmonellae and to determine the prevailing serotypes for disease burden estimations. METHODOLOGY: This involved comprehensive search engines of Pubmed, Google Scholar, Google and Embase for the literatures on culture positive human Salmonellae from 1999-2018. This review documented the prevalence, common Salmonella serotypes. antibiotic resistance and risk factors associated with human Salmonella infections. RESULTS: This study revealed that 21out of 36 States in Nigeria reported Salmonella-associated diseases, spanning the six geopolitical zones. Our study revealed prevalence of 1.9% (2,732/143,756) Salmonella-bacteraemia and 16.3% (1,967/12,081) Salmonella-associated gastroenteritis. Fifty-three 53 Salmonella serotypes were identified. 39 serotypes were associated with Salmonella-bacteraemia and 31 serotypes with Salmonella-gastroenteritis. Salmonella typhi remains the commonest serotype accounting for 85.2% for Salmonella-bacteraemia and 73.1% Salmonella-gastroenteritis. S. typhimurium (3.8%) was mostly implicated invasive non-typhoidal serotype followed S. enteritidis (2.8%) among others. Human Immunodeficiency Virus-infected individuals, malnutrition was among factors predisposing Salmonella infections. Over 60% of the reported Salmonella isolates developed resistance to two or more of 23 antibiotics recorded, mostly ampicillin, cotrimoxazole, tetracycline and amoxicillin. CONCLUSIONS: This study revealed 39 Invasive and 31 non-invasive Salmonella serotypes. Ampicillin, cotrimoxazole, amoxicillin-clavulanate and tetracycline are the most frequently reported antibiotics resisted by Salmonella isolates. This antimicrobial resistance exhibited poses a threat to public health. Data generated from this review would serve as a baseline information for future surveillance studies.

The association between bowel resection and the risk of nontyphoidal salmonella infection: a nationwide propensity score-matched cohort study.

Nontyphoidal salmonella (NTS) infection has a high mortality rate. Bowel resections affect gut microbiota and immune function, and the association between bowel resection and NTS infection in human beings has not been addressed. We conducted a nationwide propensity score (PS)-matched cohort study to clarify this association. Data from the Longitudinal Health Insurance Database of Taiwan were used to establish a case-cohort with bowel resections from 2000 to 2013. Informed consent was waived by the Institutional Review Board of China Medical University Hospital (CMUH104-REC2-115) because all personal identifying information used had been de-identified. Each case was matched with one control without any bowel resection according to age, gender, index date, and propensity score (PS). Cumulative incidences of and hazard ratios (HRs) for NTS infection development were analyzed. The incidence of NTS infection was greater in patients with a bowel resection than in the control group (2.97 vs. 1.92 per 10,000 person-years), with an adjusted hazard ratio (aHR) of 1.64 (95% CI = 1.08-2.48). The incidence of NTS infection increased significantly for cases with small bowel resections and right hemicolectomies. Age (31-40 and > 50 years), hypertension, chronic kidney disease, chronic obstructive pulmonary disease, and autoimmune diseases were significant risk factors of NTS infection. Stratification analysis revealed that patients without comorbidities were prone to NTS infection after bowel resections. The increased risk of developing NTS infection could be related to the bowel resection. Specific age groups and comorbidities also contribute to increased risk of NTS infection.

Changes in the Neurochemical Characterization of Enteric Neurons in the Porcine Duodenum After Administration of Low-Dose Salmonella Enteritidis Lipopolysaccharides.

Lipopolysaccharides (LPS), also known as lipoglycans or endotoxins, form part of the outer membrane of Gram-negative bacteria. Previous studies have described the various harmful impacts of LPS on humans and animals. Nevertheless, many aspects of these effects are still not fully explained. One of them is the influence of endotoxins on the neurochemical characterization of neurons within the enteric nervous system (ENS), which is found in the intestinal wall and plays important adaptive roles during pathological processes and exposures. In this study, the impact of a low single dose of Salmonella Enteritidis LPS on the duodenal enteric neurons immunoreactive to substance P (SP), vasoactive intestinal polypeptide (VIP), pituitary adenylate cyclase activating peptide (PACAP-27), and cocaine- and amphetamine-regulated transcript (CART) was studied using a double immunofluorescence technique. During the study, it was shown that even a low dose of LPS affects the number of enteric neurons containing the neuropeptides studied, and these changes were dependent on the type of the enteric plexus. The most visible changes concerned the SP-like immunoreactive (LI) neurons in the outer submucous plexus (LPS caused an increase in the percentage of these neurons from15.74 ± 0.61 to 21.72 ± 0.79%). Furthermore, the VIP-LI neurons in the inner submucous plexus were seen to decrease from 12.64 ± 0.83 to 5.96 ± 0.58%. The mechanisms behind these noted fluctuations are not clear, but it may be connected with the pro-inflammatory and neurotoxic activity of LPS.

Clinical characteristics and predictors of community-acquired pseudomonas aeruginosa sepsis and nontyphoidal salmonella sepsis in infants: A matched Case-Control study.

BACKGROUND: Pseudomonas aeruginosa and nontyphoidal Salmonella (NTS) species may cause enteric illness with sepsis in infancy. The clinical predictors distinguishing the two pathogens have not been comprehensively evaluated in this population in Taiwan. METHODS: A retrospective matched case-control study was conducted in a teaching hospital in southern Taiwan from January 1, 2003 to January 30, 2019. The patients with community-acquired P. aeruginosa sepsis were matched at a ratio of 1:2 by age and gender with controls (who developed NTS sepsis). RESULTS: A total of 21 infants with community-acquired P. aeruginosa sepsis were identified; of these, 12 (57.1%) were male, and the mean ± standard deviation of age was 6.95 ± 2.47 months. Two independent predictors indicative of P. aeruginosa sepsis, as identified by multivariate analysis using conditional logistic regression, were hemoglobin level (Hb) (matched odds ratio [mOR], 0.155; 95% confidence interval [CI], 0.027-0.900; p = 0.038) and platelet count (mOR, 0.988, 95% CI, 0.976-1.000; p = 0.049). The areas under the receiver operating characteristic (ROC) curves of Hb and platelet count for P. aeruginosa sepsis prediction were 0.855 and 0.803, respectively. With cut-off values for Hb of 10.7 g/dL and platelet count of 173,000/µL, the predictors had maximal diagnostic accuracy. CONCLUSION: Most patients with P. aeruginosa sepsis are less than one year old. A lower hemoglobin level and a lower platelet count are significant predictors of P. aeruginosa sepsis. These findings should help to reshape the policy of empirical antibiotics in infants with sepsis.

Characteristics and outcomes of osteomyelitis in children with sickle cell disease: A 10-year single-center experience.

BACKGROUND: Patients with sickle cell disease (SCD) are at increased risk for osteomyelitis (OM). Diagnosis of OM in SCD is challenging as the clinical presentation is similar to a vasoocclusive crisis (VOC) with no diagnostic gold standard. We report characteristics and outcomes of OM in SCD patients treated at our center over 10-year period. DESIGN/METHOD: We conducted a retrospective analysis of patients with SCD who were treated for OM at our center over a 10-year period (2006-2016). Cases were identified utilizing radiology data mining software. Radiology reports and medical charts of potential OM cases were reviewed. RESULTS: Twenty-eight children with SCD were treated for OM at our institution. Patients treated for OM were largely similar to patients treated for a VOC. However, patients treated for OM had significantly higher C-reactive protein (10 mg/dL vs 5.58 mg/dL, P = 0.03) and erythrocyte sedimentation rate (60 mm/h vs 47 mm/h, P = 0.02). Magnetic resonance imaging (MRI) findings were consistent with OM in 18 (64%) patients and indeterminate in the remaining. Based on clinical, laboratory, and radiological findings, the diagnosis of OM was considered confirmed in 3 patients, probable in 6 patients, and presumed in 19 patients. Nontyphoidal Salmonella was isolated from cultures in 9 (32%) patients, while no organism was identified in 19 (67%) patients. All patients were treated with antibiotics. Six patients (21%) required surgical interventions. CONCLUSIONS: OM continues to pose diagnostic challenges. Most patients are treated for OM without definitive confirmation. Nontyphoidal Salmonella was the only organism identified in our cohort.

Increased intracellular survival of Salmonella Typhimurium ST313 in HIV-1-infected primary human macrophages is not associated with Salmonella hijacking the HIV compartment.

BACKGROUND: Non-typhoidal Salmonella (NTS) causes a severe invasive syndrome (iNTS disease) described in HIV-positive adults. The impact of HIV-1 on Salmonella pathogenesis and the molecular basis for the differences between these bacteria and classical diarrhoeal S. Typhimurium remains unclear. RESULTS: Here, we show that iNTS-associated S. Typhimurium Sequence Type 313 (ST313) bacteria show greater intracellular survival in primary human macrophages, compared with a 'classical' diarrhoeal S. Typhimurium ST19 isolate. The increased intracellular survival phenotype of ST313 is more pronounced in HIV-infected macrophages. We explored the possibility that the bacteria take advantage of the HIV-associated viral-containing compartments created in human macrophages that have low pH. Confocal fluorescence microscopy and focussed ion beam-scanning electron microscopy tomography showed that Salmonella did not co-localise extensively with HIV-positive compartments. CONCLUSION: The capacity of ST313 bacteria to survive better than ST19 bacteria within primary human macrophages is enhanced in cells pre-infected with HIV-1. Our results indicate that the ST313 bacteria do not directly benefit from the niche created by the virus in HIV-1-infected macrophages, and that they might take advantage from a more globally modified host cell. SIGNIFICANCE: A better understanding of the interplay between HIV-1 and Salmonella is important not only for these bacteria but also for other opportunistic pathogens.

Salmonella and Reactive Oxygen Species: A Love-Hate Relationship.

Salmonella enterica represents an enterobacterial species including numerous serovars that cause infections at, or initiated at, the intestinal epithelium. Many serovars also act as facultative intracellular pathogens with a tropism for phagocytic cells. These bacteria not only survive in phagocytes but also undergo de facto replication therein. Phagocytes, through the activities of phagocyte NADPH-dependent oxidase and inducible nitric oxide synthase, are very proficient in converting molecular oxygen to reactive oxygen (ROS) and nitrogen species (RNS). These compounds represent highly efficient effectors of the innate immune defense. Salmonella is by no means resistant to these effectors, which may stand in contrast to the host niches chosen. To cope with this paradox, these bacteria rely on an array of detoxification and repair systems. Combination these systems allows for a high enough tolerance to ROS and RNS to enable establishment of infection. In addition, salmonella possesses protein factors that have the potential to dampen the infection-associated inflammation, which evidently results in a reduced exposure to ROS and RNS. This review attempts to summarize the activities and strategies by which salmonella tries to cope with ROS and RNS and how the bacterium can make use of these innate defense factors.

A Gut Commensal-Produced Metabolite Mediates Colonization Resistance to Salmonella Infection.

The intestinal microbiota provides colonization resistance against pathogens, limiting pathogen expansion and transmission. These microbiota-mediated mechanisms were previously identified by observing loss of colonization resistance after antibiotic treatment or dietary changes, which severely disrupt microbiota communities. We identify a microbiota-mediated mechanism of colonization resistance against Salmonella enterica serovar Typhimurium (S. Typhimurium) by comparing high-complexity commensal communities with different levels of colonization resistance. Using inbred mouse strains with different infection dynamics and S. Typhimurium intestinal burdens, we demonstrate that Bacteroides species mediate colonization resistance against S. Typhimurium by producing the short-chain fatty acid propionate. Propionate directly inhibits pathogen growth in vitro by disrupting intracellular pH homeostasis, and chemically increasing intestinal propionate levels protects mice from S. Typhimurium. In addition, administering susceptible mice Bacteroides, but not a propionate-production mutant, confers resistance to S. Typhimurium. This work provides mechanistic understanding into the role of individualized microbial communities in host-to-host variability of pathogen transmission.

The importance of wild gecko as a source of human Salmonella infection.

A total of 201 wild geckos from the region of Mekong Delta, Vietnam were collected to determine the viable number and survival period of Salmonella in their feces. Of the 101 samples examined, 24 (23.8%) were Salmonella positive. These 24 geckos excreted Salmonella in their feces in a range of 1 to 8.6 log CFU/g with a mean of 4.5 ± 3.2 log CFU/g. Among the Salmonella serovars, Salmonella Weltevreden was the most predominant serovar (37.5%). Moreover, Salmonella could survive for 6 weeks in gecko feces at room temperature in Vietnam. These results indicate that the wild gecko seems to play an important role as a reservoir for Salmonella and a source of Salmonella infection in humans in Southeast Asian countries.

Presentation of life-threatening invasive nontyphoidal Salmonella disease in Malawian children: A prospective observational study.

Nontyphoidal Salmonellae commonly cause invasive disease in African children that is often fatal. The clinical diagnosis of these infections is hampered by the absence of a clear clinical syndrome. Drug resistance means that empirical antibiotic therapy is often ineffective and currently no vaccine is available. The study objective was to identify risk factors for mortality among children presenting to hospital with invasive Salmonella disease in Africa. We conducted a prospective study enrolling consecutive children with microbiologically-confirmed invasive Salmonella disease admitted to Queen Elizabeth Central Hospital, Blantyre, in 2006. Data on clinical presentation, co-morbidities and outcome were used to identify children at risk of inpatient mortality through logistic-regression modeling. Over one calendar year, 263 consecutive children presented with invasive Salmonella disease. Median age was 16 months (range 0-15 years) and 52/256 children (20%; 95%CI 15-25%) died. Nontyphoidal serovars caused 248/263 (94%) of cases. 211/259 (81%) of isolates were multi-drug resistant. 251/263 children presented with bacteremia, 6 with meningitis and 6 with both. Respiratory symptoms were present in 184/240 (77%; 95%CI 71-82%), 123/240 (51%; 95%CI 45-58%) had gastrointestinal symptoms and 101/240 (42%; 95%CI 36-49%) had an overlapping clinical syndrome. Presentation at <7 months (OR 10.0; 95%CI 2.8-35.1), dyspnea (OR 4.2; 95%CI 1.5-12.0) and HIV infection (OR 3.3; 95%CI 1.1-10.2) were independent risk factors for inpatient mortality. Invasive Salmonella disease in Malawi is characterized by high mortality and prevalence of multi-drug resistant isolates, along with non-specific presentation. Young infants, children with dyspnea and HIV-infected children bear a disproportionate burden of the Salmonella-associated mortality in Malawi. Strategies to improve prevention, diagnosis and management of invasive Salmonella disease should be targeted at these children.

"Does the Salmonella Genomic Island 1 (SGI1) confer invasiveness properties to human isolates?"

BACKGROUND: In the eighties, a multidrug resistant clone of Salmonella Typhimurium DT104 emerged in UK and disseminated worldwide. This clone harbored a Salmonella genomic island 1 (SGI1) that consists of a backbone and a multidrug resistant region encoding for penta-resistance (ampicillin, chloramphenicol/florfenicol, streptomycin/spectinomycin, sulphonamides and tetracycline (ACSSuT)). Several authors suggested that SGI1 might have a potential role in enhancement of virulence properties of Salmonella enterica. The aim of this study was to investigate whether nontyphoidal S. enterica isolates carrying SGI1 cause more severe illness than SGI1 free ones in humans. METHODS: From 2011 to 2016, all patients infected with nontyphoidal S. enterica in our hospital were retrospectively included. All nontyphoidal S. enterica isolates preserved in our University Hospital (Dijon, France) were screened for the presence of SGI1. Clinical and biological data of patients were retrospectively collected to evaluate illness severity. Statistical analysis of data was performed by Kruskal-Wallis test or Fisher's exact test for univariate analysis, and by logistic regression for multivariate analysis. RESULTS: A total of 100 isolates of S. enterica (22 serovars) were collected. Twelve isolates (12%) belonging to 4 serovars harbored SGI1: S. Typhimurium, S. Infantis, S. Kentucky, S. St Paul. The severity of the disease was age-related (for invasive infection, sepsis and inflammatory response) and was associated with immunosuppression (for invasive infection, sepsis and bacteremia) but not with the presence of SGI1 or with antimicrobial resistance. CONCLUSION: A rather high proportion (12%) of human clinical isolates belonging to various serovars (for the first time serovar St Paul) and harboring various antimicrobial resistance profile carried SGI1. Diseases due to SGI1-positive S. enterica or to antimicrobial resistant isolates were not more severe than the others. This first clinical observation should be confirmed by a multicenter and prospective study.

Water Quality Survey of Splash Pads After A Waterborne Salmonellosis Outbreak--Tennessee, 2014.

Waterborne outbreaks of salmonellosis are uncommon. The Tennessee Department of Health investigated a salmonellosis outbreak of 10 cases with the only common risk factor being exposure to a single splash pad. Risks included water splashed in the face at the splash pad and no free residual chlorine in the water system. We surveyed water quality and patron behaviors at splash pads statewide. Of the 29 splash pads participating in the water quality survey, 24 (83%) used a recirculating water system. Of the 24, 5 (21%) water samples were tested by polymerase chain reaction and found to be positive for E. coli, Giardia, norovirus, or Salmonella. Among 95 patrons observed, we identified common high-risk behaviors of sitting on the fountain or spray head and putting mouth to water. Water venue regulations and improved education of patrons are important to aid prevention efforts.

Ground water as the source of an outbreak of Salmonella Enteritidis.

In September 2014, an outbreak of gastroenteritis was reported to the Public Health Institute of Sibenik and Knin County in Croatia. The outbreak occurred in the County center of Sibenik, a town with 50,000 inhabitants, and it lasted for 12days. An epidemiological investigation suggested a nearby water spring as the source of the outbreak. Due to the temporary closure of the public water supply system, the inhabitants started to use untreated water from a nearby spring. Microbiological analysis revealed that the outbreak was caused by Salmonella enterica subsp. enterica serovar Enteritidis that was isolated from stool samples of the patients and ground water. The isolates were further analysed with pulsed-field gel electrophoresis using XbaI, which revealed an identical macrorestriction profile. Although 68 cases were reported, it was estimated that the actual number of affected persons was more than several hundred. In order to prevent further spread of disease, public advice was released immediately after the first epidemiological indication and a warning sign was placed at the incriminated water source, after microbiological confirmation. It is necessary to regularly monitor microbiological quality of ground water especially in urban areas and provide adequate education and awareness to the inhabitants regarding the risk of using untreated ground water.

Clinical-associated characteristics and microbiological features of bloodstream nontyphoidal salmonella infection in adult patients receiving allogeneic hematopoietic stem cell transplantation.

Bloodstream nontyphoidal salmonella (NTS) infection is rare, but its associated characteristics and microbiological features in immunocompromised patients are worth paying attention to, particularly for those receiving allogeneic hematopoietic stem cell transplantation (SCT). No studies so far have analyzed post-transplant bloodstream NTS infection. Therefore, we reviewed 423 adult patients undergoing allogeneic hematopoietic SCT from 2003 to 2014. Nine out of four hundred twenty-three patients (2.13%) developed post-transplant bloodstream NTS infection, including two patients who had subsequent or combined metastatic infections. The median age at SCT was 35 years (interquartile range, 29-46) among the nine patients with bloodstream NTS infection. Male patients were predominant (78%). The median onset of bloodstream NTS infection was at 315 days after SCT (range, 207-629). Multivariate analysis revealed that extensive chronic graft-versus-host disease (GVHD) (OR 8.054, p = 0.003) and nonmyeloablative transplant conditioning (OR 4.604, p = 0.037) were significant associated characteristics for NTS infection. Currently, there are no published data analyzing and exploring post-transplant bloodstream NTS infections in adult allogeneic hematopoietic SCT. Our study determined the associated characteristics and microbiological features for this infection.

An association between decreasing incidence of invasive non-typhoidal salmonellosis and increased use of antiretroviral therapy, Gauteng Province, South Africa, 2003-2013.

BACKGROUND: HIV-infected persons are at increased risk of opportunistic infections, including invasive nontyphoidal Salmonella (iNTS) infections; antiretroviral therapy (ART) reduces this risk. We explored changing iNTS incidence associated with increasing ART availability in South Africa. METHODS: Laboratory-based surveillance for iNTS was conducted in Gauteng Province, South Africa, with verification using the National Health Laboratory Service's Central Data Warehouse (CDW), between 2003 and 2013. Isolates were serotyped at the Centre for Enteric Diseases. CDW data on patient numbers obtaining HIV viral load measurements provided estimates of numbers of HIV-infected patients receiving ART. A Poisson regression model was used to measure the changing incidence of iNTS infection from 2003 to 2013. The correlation between the incidence of iNTS and ART use from 2004 to 2013 was determined using Pearson's correlation coefficient. RESULTS: From 2003-2013, the incidence of iNTS per 100,000 population per year decreased from 5.0 to 2.2 (p < .001). From 2004 to 2013, the incidence per 100,000 population of HIV viral load testing increased from 75.2 to 3,620.3 (p < .001). The most common serotypes causing invasive disease were Salmonella enterica serovar Typhimurium (Salmonella Typhimurium), and Salmonella Enteritidis: 2,469 (55.4%) and 1,156 (25.9%) of 4,459 isolates serotyped, respectively. A strong negative correlation was observed between decreasing iNTS incidence and increasing ART use from 2004 to 2013 (r = -0.94, p < .001). Similarly, decreasing incidence of invasive Salmonella Typhimurium infection correlated with increasing ART use (r = -0.93, p < .001). Incidence of invasive Salmonella Enteritidis infection increased, however (r = 0.95, p < .001). Between 2003 and 2004, fewer adult men than women presented with iNTS (male-to-female rate ratio 0.73 and 0.89, respectively). This was reversed from 2005 through 2013 (ranging from 1.07 in 2005 to 1.44 in 2013). Adult men accessed ART less (male-to-female rate ratio ranging from 0.61 [2004] to 0.67 [2013]). CONCLUSIONS: The incidence of iNTS infections including Salmonella Typhimurium decreased significantly in Gauteng Province in association with increased ART utilization. Adult men accessed ART programs less than women, translating into increasing iNTS incidence in this group. Monitoring iNTS incidence may assist in monitoring the ART program. Increasing incidence of invasive Salmonella Enteritidis infections needs further elucidation.