Effect of biannual azithromycin distribution on antibody responses to malaria, bacterial, and protozoan pathogens in Niger.

The MORDOR trial in Niger, Malawi, and Tanzania found that biannual mass distribution of azithromycin to children younger than 5 years led to a 13.5% reduction in all-cause mortality (NCT02048007). To help elucidate the mechanism for mortality reduction, we report IgG responses to 11 malaria, bacterial, and protozoan pathogens using a multiplex bead assay in pre-specified substudy of 30 communities in the rural Niger placebo-controlled trial over a three-year period (n = 5642 blood specimens, n = 3814 children ages 1-59 months). Mass azithromycin reduces Campylobacter spp. force of infection by 29% (hazard ratio = 0.71, 95% CI: 0.56, 0.89; P = 0.004) but serological measures show no significant differences between groups for other pathogens against a backdrop of high transmission. Results align with a recent microbiome study in the communities. Given significant sequelae of Campylobacter infection among preschool aged children, our results support an important mechanism through which biannual mass distribution of azithromycin likely reduces mortality in Niger.

Baseline iron status and presence of anaemia determine the course of systemic Salmonella infection following oral iron supplementation in mice.

BACKGROUND: Iron deficiency anaemia (IDA) is a major health concern. However, preventive iron supplementation in regions with high burden of infectious diseases resulted in an increase of infection related morbidity and mortality. METHODS: We fed male C57BL/6N mice with either an iron deficient or an iron adequate diet. Next, they received oral iron supplementation or placebo followed by intraperitoneal infection with Salmonella Typhimurium (S.Tm). FINDINGS: We found that mice with IDA had a poorer clinical outcome than mice on an iron adequate diet. Interestingly, iron supplementation of IDA mice resulted in higher bacterial burden in organs and shortened survival. Increased transferrin saturation and non-transferrin bound iron in the circulation together with low expression of ferroportin facilitated the access of the pathogen to iron and promoted bacterial growth. Anaemia, independent of iron supplementation, was correlated with reduced neutrophil counts and cytotoxic T cells. With iron supplementation, anaemia additionally correlated with increased splenic levels of the cytokine IL-10, which is suggestive for a weakened immune control to S.Tm infection. INTERPRETATION: Supplementing iron to anaemic mice worsens the clinical course of bacterial infection. This can be traced back to increased iron delivery to bacteria along with an impaired anti-microbial immune response. Our findings may have important implications for iron supplementation strategies in areas with high endemic burden of infections, putting those individuals, who potentially profit most from iron supplementation for anaemia, at the highest risk for infections. FUNDING: Financial support by the Christian Doppler Laboratory for Iron Metabolism and Anemia Research.

Salmonella Bloodstream Infections in Hospitalized Children with Acute Febrile Illness-Uganda, 2016-2019.

Invasive Salmonella infection is a common cause of acute febrile illness (AFI) among children in sub-Saharan Africa; however, diagnosing Salmonella bacteremia is challenging in settings without blood culture. The Uganda AFI surveillance system includes blood culture-based surveillance for etiologies of bloodstream infection (BSIs) in hospitalized febrile children in Uganda. We analyzed demographic, clinical, blood culture, and antimicrobial resistance data from hospitalized children at six sentinel AFI sites from July 2016 to January 2019. A total of 47,261 children were hospitalized. Median age was 2 years (interquartile range, 1-4) and 26,695 (57%) were male. Of 7,203 blood cultures, 242 (3%) yielded bacterial pathogens including Salmonella (N = 67, 28%), Staphylococcus aureus (N = 40, 17%), Escherichia spp. (N = 25, 10%), Enterococcus spp. (N = 18, 7%), and Klebsiella pneumoniae (N = 17, 7%). Children with BSIs had longer median length of hospitalization (5 days versus 4 days), and a higher case-fatality ratio (13% versus 2%) than children without BSI (all P < 0.001). Children with Salmonella BSIs did not differ significantly in length of hospitalization or mortality from children with BSI resulting from other organisms. Serotype and antimicrobial susceptibility results were available for 49 Salmonella isolates, including 35 (71%) non-typhoidal serotypes and 14 Salmonella serotype Typhi (Typhi). Among Typhi isolates, 10 (71%) were multi-drug resistant and 13 (93%) had decreased ciprofloxacin susceptibility. Salmonella strains, particularly non-typhoidal serotypes and drug-resistant Typhi, were the most common cause of BSI. These data can inform regional Salmonella surveillance in East Africa and guide empiric therapy and prevention in Uganda.

One-step differential detection of Salmonella enterica serovar Typhi, serovar Paratyphi A and other Salmonella spp. by using a quadruplex real-time PCR assay.

Diseases caused by typhoidal and non-typhoidal Salmonella remain a considerable threat to both developed and developing countries. Based on the clinical symptoms and serological tests, it is sometimes difficult to differentiate the Salmonella enterica serovar Paratyphi A (S. enterica serovar Paratyphi A) from serovar Typhi (S. enterica serovar Typhi). In this study, we developed a quadruplex real-time polymerase chain reaction (PCR) assay with an internal amplification control (IAC), to simultaneously differentiate S. enterica serovar Paratyphi A from serovar Typhi and to detect other Salmonella serovars which cause salmonellosis in humans. This assay was evaluated on 155 salmonellae and non-salmonellae strains and demonstrated 100% specificity in species differentiation. Inclusion of an IAC did not affect the efficiency of the assay. Further evaluation using a blind test on spiked stool, blood and food specimens showed that the detection limit was at 103 -104 CFU/mL (or g) and a high PCR efficiency with different targets (R2 > 0.99), except for S. enterica serovar Paratyphi A in blood. This assay has been applied to clinical specimens to detect the causative agents of gastrointestinal infections and has successfully identified 6 salmonellosis patients from the 50 diarrhoea patients. The quadruplex real-time PCR developed in this study could enhance the detection and differentiation of salmonellae. This assay could be applied to stools, blood and food based on the notable performance in the simulation tests and field evaluation.

Downregulation of a novel flagellar synthesis regulator AsiR promotes intracellular replication and systemic pathogenicity of Salmonella typhimurium.

The intracellular pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium) exploits host macrophage as a crucial survival and replicative niche. To minimize host immune response stimulated by flagellin, the expression of flagellar genes is downregulated during S. Typhimurium growth within host macrophages. However, the underlying mechanisms are largely unknown. In this study, we show that STM14_1285 (named AsiR), a putative RpiR-family transcriptional regulator, which is downregulated within macrophages as previously reported and also confirmed here, positively regulates the expression of flagellar genes by directly binding to the promoter of flhDC. By generating an asiR mutant strain and a strain that persistently expresses asiR gene within macrophages, we confirmed that the downregulation of asiR contributes positively to S. Typhimurium replication in macrophages and systemic infection in mice, which could be attributed to decreased flagellar gene expression and therefore reduced flagellin-stimulated secretion of pro-inflammatory cytokines IL-1ß and TNF-α. Furthermore, the acidic pH in macrophages is identified as a signal for the downregulation of asiR and therefore flagellar genes. Collectively, our results reveal a novel acidic pH signal-mediated regulatory pathway that is utilized by S. Typhimurium to promote intracellular replication and systemic pathogenesis by repressing flagellar gene expression.

High relatedness of invasive multi-drug resistant non-typhoidal Salmonella genotypes among patients and asymptomatic carriers in endemic informal settlements in Kenya.

Invasive Non-typhoidal Salmonella (iNTS) disease is a major public health challenge, especially in Sub-Saharan Africa (SSA). In Kenya, mortality rates are high (20-25%) unless prompt treatment is instituted. The most common serotypes are Salmonella enterica serotype Typhimurium (S. Typhimurium) and Salmonella enterica serotype Enteritidis (S. Enteritidis). In a 5 year case-control study in children residing in the Mukuru informal settlement in Nairobi, Kenya, a total of 4201 blood cultures from suspected iNTS cases and 6326 fecal samples from age-matched controls were studied. From the laboratory cultures we obtained a total of 133 S. Typhimurium isolates of which 83(62.4%) came from cases (53 blood and 30 fecal) and 50(37.6%) from controls (fecal). A total of 120 S. Enteritidis consisted of 70(58.3%) from cases (43 blood and 27 fecal) and 50(41.7%) from controls (fecal). The S. Typhimurium population fell into two distinct ST19 lineages constituting 36.1%, as well as ST313 lineage I (27.8%) and ST313 lineage II (36.1%) isolates. The S. Enteritidis isolates fell into the global epidemic lineage (46.6%), the Central/Eastern African lineage (30.5%), a novel Kenyan-specific lineage (12.2%) and a phylogenetically outlier lineage (10.7%). Detailed phylogenetic analysis revealed a high level of relatedness between NTS from blood and stool originating from cases and controls, indicating a common source pool. Multidrug resistance was common throughout, with 8.5% of such isolates resistant to extended spectrum beta lactams. The high rate of asymptomatic carriage in the population is a concern for transmission to vulnerable individuals and this group could be targeted for vaccination if an iNTS vaccine becomes available.

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.

Sensitive detection of a bacterial pathogen using allosteric probe-initiated catalysis and CRISPR-Cas13a amplification reaction.

The ability to detect low numbers of microbial cells in food and clinical samples is highly valuable but remains a challenge. Here we present a detection system (called 'APC-Cas') that can detect very low numbers of a bacterial pathogen without isolation, using a three-stage amplification to generate powerful fluorescence signals. APC-Cas involves a combination of nucleic acid-based allosteric probes and CRISPR-Cas13a components. It can selectively and sensitively quantify Salmonella Enteritidis cells (from 1 to 105 CFU) in various types of samples such as milk, showing similar or higher sensitivity and accuracy compared with conventional real-time PCR. Furthermore, APC-Cas can identify low numbers of S. Enteritidis cells in mouse serum, distinguishing mice with early- and late-stage infection from uninfected mice. Our method may have potential clinical applications for early diagnosis of pathogens.

MDR Salmonella enterica serovar Typhimurium ST34 carrying mcr-1 isolated from cases of bloodstream and intestinal infection in children in China.

OBJECTIVES: Children are vulnerable to Salmonella infection due to their immature immune system. Cases of infection with mcr-1-harbouring Salmonella in child inpatients have not been reported in China before. METHODS: Salmonella isolates from gastroenteritis and bacteraemia were screened using primers targeting mcr-1. Complete genome sequences of mcr-1-harbouring isolates were determined using the PacBio RS II platform. The transferability of mcr-1-harbouring plasmids was verified by conjugation. RESULTS: We investigated two mcr-1-carrying polymyxin-resistant Salmonella enterica serovar Typhimurium ST34 isolates, S61394 and S44712, from bloodstream and intestinal Salmonella infection of two child inpatients, respectively. Both isolates were non-susceptible to commonly used antibiotics for children that compromised the success of clinical treatment and infection control. The mcr-1-harbouring plasmids pLS61394-MCR and pLS44712-MCR (from S61394 and S44712, respectively) were both conjugative pHNSHP45-2-like IncHI2-type epidemic plasmids carrying multiple resistance genes. Compared with pHNSHP45-2, a ∼33 kb insertion region encoding Tn7 transposition protein and heavy metal resistance proteins was identified in pLS61394-MCR, which might enhance adaptation of bacteria carrying this plasmid to various ecological niches. The phylogenetic tree of worldwide mcr-harbouring Salmonella indicated a host preference of mcr and a worldwide and cross-sectoral prevalence of the mcr-positive Salmonella ST34 clone. CONCLUSIONS: To our knowledge, for the first time we report completed whole genomes of mcr-1-positive MDR Salmonella Typhimurium ST34 isolated from infected children in China, suggesting that improved surveillance is imperative for tackling the dissemination of mcr-harbouring MDR Salmonella Typhimurium ST34.

Risk Factors for Nontyphi Salmonella Bacteremia Over 10 Years in Fort-de-France, Martinique, West Indies.

Nontyphoidal Salmonella infections can result in bacteremia. This study was undertaken to determine the predictive factors for bacteremia in children aged less than 16 years. Medical data were collected for every child with positive nontyphoidal Salmonella cultures in blood or stools at the University hospital of Martinique, French West Indies, between January 2005 and December 2015. Among 454 patients, 333 were included; 156 cases had confirmed bacteremia, and 177 were included as control group with nontyphoidal Salmonella only isolated in stools. Age at diagnosis, delay before consulting, prematurity, immunosuppression, or hyperthermic seizures were not significantly associated with bacteremia. C-reactive protein was higher in cases of bacteremia (P = 0.01); however, after adjusting to the threshold of 30 mg/L, there was no longer any difference. There were also significant relations for electrolytes such as hyponatremia (odds ratio (OR) = 2.08 [95% CI = 1.31-3.95]; P < 0.01), high urea level (OR = 0.53 [95% CI = 0.32-0.88], P < 0.01). The infecting serotype was the most discriminant risk factor (P < 10-4). Among 28 serotypes isolated between 2005 and 2015, Salmonella panama was the most common serotype: 122 strains (78.2%) were isolated from bacteremic patients versus 60 (33.9%) from nonbacteremic patients (P < 10-4). Salmonella panama was the most important risk factor for bacteremia (OR = 7.37 [95% CI = 3.18-17.1], P < 10-4) even after multivariate analysis (OR = 13.09 [95% CI = 5.42-31.59], P < 10-4). After adjusting for bacteremia, S. panama was associated with a significantly higher body temperature than other Salmonella: 39°C (standard deviation [SD] = 0.92) versus 38.2°C [SD = 1.1], linear regression P < 10-3. Children with Salmonella serotype panama infection were at higher risk of bacteremia than children infected with other Salmonella serotypes.

Increasing incidence of invasive nontyphoidal Salmonella infections in Queensland, Australia, 2007-2016.

Nontyphoidal Salmonella is a major contributor to the global burden of foodborne disease, with invasive infections contributing substantially to illnesses and deaths. We analyzed notifiable disease surveillance data for invasive nontyphoidal Salmonella disease (iNTS) in Queensland, Australia. We used Poisson regression to estimate incidence rate ratios by gender, age group, and geographical area over 2007-2016. There were 995 iNTS cases, with 945 (92%) confirmed by blood culture. Salmonella Virchow accounted for 254 (25%) of 1,001 unique iNTS isolates. Invasive NTS disease notification rates peaked among infants, during the summer months, and in outback Queensland where the notification rate (95% CI) was 17.3 (14.5-20.1) cases per 100,000 population. Overall, there was a 6,5% annual increase (p<0.001) in iNTS disease incidence. In conclusion, high iNTS rates among males, infants, and the elderly require investigation of household level risk factors for NTS infection. Controlling Salmonella Virchow infections is a public health priority.

Salmonella enterica serovar enteritidis peritonitis with spontaneous intestinal perforation in an immunocompetent patient.

Few data reported non-typhoidal Salmonella peritonitis in immunocompromised patients. We reported the case of a man without immunosuppression or predisposing factor, who developed Salmonella enterica serovar Enteritidis peritonitis with spontaneous intestinal perforation. After emergent surgery, the patient was transferred to intensive care unit (ICU) because of respiratory, renal and haemodynamic failures. When S. enterica serovar Enteritidis was identified, antibiotics were de-escalated for ceftriaxone and metronidazole for 5 days. No immunosuppression was found. Evolution was favourable, and the patient has been discharged from the ICU on day 8. The originality of this case arises from a perforation peritonitis secondary to S. enterica without any immunosuppression. In absence of non-Typhi Salmonella data, we treated this patient as a typhoid perforation: surgical treatment, antibiotic association and supportive care.

Epidemiology and Antimicrobial Susceptibility of Salmonella enterica Bloodstream Isolates Among Febrile Children in a Rural District in Northeastern Tanzania: A Cross-sectional Study.

BACKGROUND: Salmonella enterica including Salmonella Typhi and nontyphoidal Salmonella (NTS) are the predominant cause of community-acquired bloodstream infections in sub-Saharan Africa (sSA). Multiple-drug resistance and emerging fluoroquinolone resistance are of concern. Data on the age distribution of typhoid fever in sSA are scarce but essential for typhoid conjugate vaccine policy. We sought to describe Salmonella bloodstream infections, antimicrobial resistance, and age distribution at a rural district hospital in northeastern Tanzania. METHODS: From 2008 to 2016, febrile children or children with a history of fever aged 1 month to 5 years admitted to Korogwe District Hospital were enrolled. Demographic, clinical data and blood cultures were collected. Organisms were identified by conventional microbiological methods, and antimicrobial susceptibility test was done by disc diffusion. RESULTS: Of 4176 participants receiving blood cultures, 383 (9.2 %) yielded pathogens. Of pathogens, 171 (44.6%) were Salmonella enterica of which 129 (75.4%) were Salmonella Typhi, and 42 (24.6%) were NTS. The median (interquartile range age of participants was 13.1 (6.3-28.0) months for those with Salmonella Typhi and 11.5 (8.5-23.4) months for NTS. Of 129 Salmonella Typhi, 89 (89.9%) were resistant to amoxicillin, 85 (81.0%) to chloramphenicol, and 93 (92.1%) to trimethoprim-sulfamethoxazole compared with 22 (62.9%), 15 (39.4%), and 27 (79.4%), respectively, for NTS. Multidrug resistance was present in 68 (81.0%) of Salmonella Typhi and 12 (41.4%) of NTS. CONCLUSION: Salmonella Typhi was the leading cause of bloodstream infection among infants and young children <2 years of age admitted to Korogwe District Hospital. Multidrug resistance was common, highlighting a role for typhoid conjugate vaccine into routine infant vaccine schedules.

The global burden and epidemiology of invasive non-typhoidal Salmonella infections.

Invasive non-typhoidal Salmonella (iNTS) disease has emerged as a major public health concern. Yet, understanding of the global burden is incomplete, limited particularly by the breadth of blood culture-based surveillance systems that are able to accurately diagnose the etiology of bacteremia. The accessibility of whole genome sequencing has allowed for genetic characterization of pathogens, shedding light on its evolutionary history and sounding alerts for its future progression. iNTS disease is observed to be a particular threat in sub-Saharan Africa, with a case fatality rate greatly exceeding that of typhoid fever, and commonly affecting infants, young children and immunocompromised adults. While iNTS disease might also be a threat in Asia and Latin America, its burden is not well characterized, primarily owing to the lack of comprehensive reporting in these regions. Drug-resistant Salmonella enterica (S. enterica) serovars (e.g. Typhimurium sequence type 313 (ST313)) have emerged as a potential consequence of sustained antibiotic pressure. Genetic analyses have identified distinguished iNTS disease-causing strains that are particularly virulent in certain human host populations. Effective treatment strategies, including vaccination, are necessary; iNTS vaccines targeting the most common S. enterica serovars, Typhimurium, Enteritidis and Dublin, are currently in early developmental stages. Funding and political support is needed to promote vaccine development and implementation programs to ultimately reduce the threat of iNTS disease in high risk areas.

Accelerated Aging and Clearance of Host Anti-inflammatory Enzymes by Discrete Pathogens Fuels Sepsis.

Sepsis is a life-threatening inflammatory syndrome accompanying a bloodstream infection. Frequently secondary to pathogenic bacterial infections, sepsis remains difficult to treat as a singular disease mechanism. We compared the pathogenesis of murine sepsis experimentally elicited by five bacterial pathogens and report similarities among host responses to Gram-negative Salmonella and E. coli. We observed that a host protective mechanism involving de-toxification of lipopolysaccharide by circulating alkaline phosphatase (AP) isozymes was incapacitated during sepsis caused by Salmonella or E. coli through activation of host Toll-like receptor 4, which triggered Neu1 and Neu3 neuraminidase induction. Elevated neuraminidase activity accelerated the molecular aging and clearance of AP isozymes, thereby intensifying disease. Mice deficient in the sialyltransferase ST3Gal6 displayed increased disease severity, while deficiency of the endocytic lectin hepatic Ashwell-Morell receptor was protective. AP augmentation or neuraminidase inhibition diminished inflammation and promoted host survival. This study illuminates distinct routes of sepsis pathogenesis, which may inform therapeutic development.

Salmonella enterica serovars Panama and Arechavaleta: Risk Factors for Invasive Non-Typhoidal Salmonella Disease in Guadeloupe, French West Indies.

A retrospective study was conducted to identify the risk factors associated with Salmonella enterica bacteremia in infants and children in Guadeloupe, French West Indies. The 171 patients with S. enterica infection seen between 2010 and 2014 included 155 (90.6%) with acute gastroenteritis, of whom 42 (27.1%) had concomitant bacteremia, and 16 (9.4%) with primary bacteremia. Most cases (97.7%) were in infants and children with no underlying health condition. Two subspecies were recovered: enterica (N = 161, 94.2%) and houtenae (N = 10, 5.8%). All but one (serovar Typhi) were non-typhoidal Salmonella. The most common serovars were Panama (N = 57, 33.3% of isolates) and Arechavaleta (N = 28, 16.4%). Univariate analysis showed a strong association only between age > 6 months and infection with the Panama or Arechavaleta serovar (P = 0.002). The rate of resistance to all classes of antibiotics during the study period was low (< 15%); however, the detection of one extended-spectrum beta-lactamase-producing S. enterica strain highlights the need for continued monitoring of antimicrobial drug susceptibility. Infection with Panama (P < 0.001) or Arechavaleta (P < 0.001) serovar was significantly associated with bacteremia in a multivariate analysis. These serovars are probably poorly adapted to humans or are more virulent. A delay between onset of symptoms and hospital admission > 5 days (P = 0.01), vomiting (P = 0.001), and increased respiratory rate (P = 0.001) contributed independently to bacteremia in the multivariate analysis. Thus, if non-typhoidal infection is suspected, blood should be cultured and antibiotic treatment initiated in all patients who meet these criteria.

Magnetism-Resolved Separation and Fluorescence Quantification for Near-Simultaneous Detection of Multiple Pathogens.

In the modern era of molecular evidence-based medicine and advanced biomedical technologies, the rapid, sensitive and specific assay of multiple pathogens is critical to, but largely absent from, clinical practice. Therefore, to improve the current ordinary separation and collection method, we report herein a strategy of magnetism-resolved separation and fluorescence quantification for near-simultaneous detection of multiple pathogens, followed by the direct antimicrobial susceptibility testing (AST). To accomplish this strategy, we utilized aptamer-modified fluorescent-magnetic multifunctional nanoprobes (apt-FMNPs). FMNPs with intriguing different magnetic responses and excellent fluorescence quality were first self-assembled based on metal coordination interaction using (3-mercaptopropyl) trimethoxysilane, magnetic γ-Fe2O3, and fluorescent quantum dots as matrix components. Then, aptamers, which specific to target pathogens of Escherichia coli O157:H7 ( E. coli) and Salmonella typhimurium ( S. typ), were conjugated with FMNPs to yield apt-FMNPs nanoprobes for multiple pathogens assay. Based on the discrepant magnetic response of pathogen@nanoprobes complex under the identical external magnetic field, the model bacteria were fished out by magnetic adsorption at different time points and subjected to fluorescence quantification with good linear ranges and detection limits within 1h. Multiple pathogens spiked in real samples were also effectively detected by the apt-FMNPs and sequentially fished out for AST assay, which showed similar results to that for pure pathogens. The apt-FMNPs-based strategy of near-simultaneous detection of multiple pathogens shows promise for the potential application in the diagnosis and treatment of pathogen-related infectious diseases.

Antibody titers in turkeys increase after multiple booster vaccinations with an attenuated Salmonella live vaccine.

OBJECTIVE: Human Salmonellosis is one of the most frequently reported foodborne zoonoses in the European Union. The most common source of human infections is the consumption of poultry products. Besides management and hygiene practices vaccination of poultry livestock is seen as one way to reduce Salmonella infections in humans. Turkey flocks in Europe are frequently infected with Salmonella and until recently there was no live vaccine for turkeys available. The aim of the present study was to examine the development of humoral antibodies after repeated vaccination with a bivalent live Salmonella vaccine containing attenuated Salmonella Typhimurium and Salmonella Enteritidis strains. Furthermore the colonization of the caecum with the vaccine strains and their spread to liver and spleen as well as the course of their fecal excretion was observed. RESULTS: Antibody production was hardly detectable after the first vaccination but increased after booster vaccinations. Both the Salmonella Enteritidis and the Salmonella Typhimurium vaccine strain were reisolated from caecum contents and organ samples. After booster vaccinations the re-isolation rates were reduced. The shedding of the vaccine strains was most pronounced after the first vaccination.

Diagnostic accuracy of antigen-based immunochromatographic rapid diagnostic tests for the detection of Salmonella in blood culture broth.

BACKGROUND: In low resource settings, Salmonella serovars frequently cause bloodstream infections. This study investigated the diagnostic performance of immunochromatographic rapid diagnostic tests (RDTs), which detect Salmonella antigens, when applied to stored grown blood culture broth. MATERIAL/METHODS: The SD Bioline One Step Salmonella Typhi Ag Rapid Detection Kit (Standard Diagnostics, Republic of Korea), marketed for the detection of Salmonella enterica serovar Typhi (Salmonella Typhi) in stool and the Salmonella Ag Rapid Test (Creative Diagnostics, USA), marketed for the detection of all Salmonella serotypes in stool, were selected for evaluation based on a pre-test evaluation of six RDT products. The limits of detection (LOD) for culture suspensions were established and the selected RDT products were assessed on 19 freshly grown spiked blood culture broth samples and 413 stored clinical blood culture broth samples, collected in Cambodia and the Democratic Republic of the Congo. RESULTS: The LOD of both products was established as 107-108 CFU/ml. When applied to clinical blood culture broth samples, the diagnostic sensitivity and specificity of the SD Bioline RDT were respectively 100% and 79.7% for the detection of Salmonella Typhi; 94.4% (65/69) of false-positive results were caused by Salmonella Enteritidis. When considering the combined detection of Salmonella Typhi and Enteritidis (both group D Salmonella), sensitivity and specificity were 97.9% and 98.5% respectively. For Creative Diagnostics, diagnostic sensitivity was 78.3% and specificity 91.0% for all Salmonella serotypes combined; 88.3% (53/60) of false negative results were caused by Salmonella Paratyphi A. CONCLUSIONS: When applied to grown blood culture broths, the SD Bioline RDT had a good sensitivity and specificity for the detection of Salmonella Typhi and Salmonella Enteritidis. The Creative Diagnostics product had a moderate sensitivity and acceptable specificity for the detection of all Salmonella serovars combined and needs further optimization. A RDT that reliably detects Salmonella Paratyphi A is needed.