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Pakistan Journal of Medical Sciences Jul 2024To determine the antimicrobial activity of silver nano-particles(AgNPs) with tetracycline and ampicillin against multi-drug resistance (MDR) and extensively-drug...
OBJECTIVES
To determine the antimicrobial activity of silver nano-particles(AgNPs) with tetracycline and ampicillin against multi-drug resistance (MDR) and extensively-drug resistance (XDR) .
METHODS
Cross sectional non-probability purposive study was conducted from September, 2021 to May, 2022 at Microbiology department PNS Shifa, Hospital Karachi. Blood cultures of patients suspicious of typhoid fever were collected and incubated in automated Bact/Alert system. Positive cultures were identified on blood and MacConkey and processed by API-10S, confirmed by serotyping (O9 antisera) (SSI Diagnostica's . Antibiotic resistance was done by Kirby-Bauer disk diffusion (Sigma and Rich). MDR and XDR isolates were preserved in Brain Heart Infusion in a volume of 2ml in screw capped bottles at -70°C. Antimicrobial powders (ampicillin and tetracycline (Alfa Aesar) weighed by an electrical weighing balance (OHAUS) to take 1mg of antimicrobial drug. Absorbance spectra of serial concentrations of antibiotics (UV-Vis spectrophotometer (Mole-Qule-) AgNPs (10nm) (nanocomposix) + Antibiotic in (1:1 volume ratio). Conjugation of silver nanoparticles with tetracycline and ampicillin was done by FTIR (thermos scientificThermos ScientificNicolet 50).
RESULTS
Out of 77 isolates, 54 were resistant to ceftriaxone (XDR) and 23 sensitive to ceftriaxone (MDR). All isolates were susceptible to azithromycin and meropenem. Comparison of zone of inhibitions of ampicillin and Amp-AgNPsas and tetracycline with Tet-AgNPs was done. Minimal inhibitory concentration was also done to determine antimicrobial activity.
CONCLUSION
Significant synergistic inhibitory effects against isolates were obtained by combination of tetracycline with silver nano-particles even at low concentration.
PubMed: 38952512
DOI: 10.12669/pjms.40.6.7900 -
Pakistan Journal of Medical Sciences Jul 2024This study aimed to determine the epidemiology, clinical features, and complications of extensively drug-resistant Salmonella typhi (XDR S. typhi) infection in adults.
OBJECTIVES
This study aimed to determine the epidemiology, clinical features, and complications of extensively drug-resistant Salmonella typhi (XDR S. typhi) infection in adults.
METHOD
This cross-sectional study enrolled adults with culture-proven XDR S. typhi admitted to Hayatabad Medical Complex, Peshawar from 1 March to 10 September 2022. Their demographic characteristics, clinical features, treatment, and complications were recorded.
RESULTS
Out of 84 patients, 68 (80.9%) were male. The mean age of enrolled patients was 25.2 ± 11.3 years. The mean duration of fever at the time of admission was 13.6 ± 8.2 days, respectively. The most common symptom was loose stools (n=25, 29.8%). Most of the patients (n=69, 82.1%) had received empirical treatment before hospitalization. The majority of the patients (n=42, 50%) received meropenem and a combination of meropenem and azithromycin (n=35, 41.7%) during the study. The time to defervescence for both regimens was similar. Five patients (6%) developed complications of enteric fever. There was no mortality among the participants.
CONCLUSIONS
Diarrhea was the most common associated clinical feature in XDR typhoid fever. Most of the patients received meropenem alone or in combination with azithromycin with a comparable time to defervescence. The majority of the patients recovered uneventfully and there was no mortality among the study participants.
PubMed: 38952494
DOI: 10.12669/pjms.40.6.8384 -
Public Health Jun 2024In non-endemic countries, surveillance of non-travel cases of enteric fever is important to identify carriers and reduce secondary transmission. We characterised these...
OBJECTIVES
In non-endemic countries, surveillance of non-travel cases of enteric fever is important to identify carriers and reduce secondary transmission. We characterised these cases in England between 2012 and 2021 and assessed potential sources of infection to inform guidance revision.
STUDY DESIGN
Retrospective case-case.
METHODS
We identified enteric fever cases from the national surveillance dataset. Non-travel cases were defined as no travel to an endemic country or travel but onset of >60 days after return. Multivariable logistic regression was used to identify factors associated with non-travel cases. We reviewed the case records of cases with unknown source of infection.
RESULTS
Compared to travel cases, non-travel cases (7%; 225/3075) were older (odds ratio [OR] = 1.02, 95% confidence interval [CI]: 1.02-1.04), asymptomatic (OR = 9.3: 95% CI: 4.3-20.3), and confirmed with Salmonella typhi infection (OR = 1.74, 95% CI: 1.26-2.4). Non-travel cases had lower odds of being of Indian (OR = 0.27, 95% CI: 0.16-0.45) or Pakistani ethnicity (OR = 0.34, 95% CI: 0.16-0.45) than White British. Surveillance questionnaires identified a possible infection source for 53%: case records review identified a further 23%: 33% secondary transmission, mostly household; 21% had overseas visitors, or travelling family; 12% were carriers (cases with enteric fever in the past), 12% travelled to endemic country outside of the 60-day window, and 22% had other possible sources. Case records differentiated between travel 60-90 days (5%) vs travel years prior to onset (7%), suggesting carrier status.
CONCLUSION
Not all possible carriers were identified through the surveillance questionnaire. Therefore, we recommend additional questions to systematically capture travel history beyond 60 days to assist in classifying carrier status and to updating the source of infection.
PubMed: 38945034
DOI: 10.1016/j.puhe.2024.05.035 -
Communications Biology Jun 2024Antimicrobial resistance (AMR) poses a serious threat to the clinical management of typhoid fever. AMR in Salmonella Typhi (S. Typhi) is commonly associated with the H58...
Antimicrobial resistance (AMR) poses a serious threat to the clinical management of typhoid fever. AMR in Salmonella Typhi (S. Typhi) is commonly associated with the H58 lineage, a lineage that arose comparatively recently before becoming globally disseminated. To better understand when and how H58 emerged and became dominant, we performed detailed phylogenetic analyses on contemporary genome sequences from S. Typhi isolated in the period spanning the emergence. Our dataset, which contains the earliest described H58 S. Typhi organism, indicates that ancestral H58 organisms were already multi-drug resistant (MDR). These organisms emerged spontaneously in India in 1987 and became radially distributed throughout South Asia and then globally in the ensuing years. These early organisms were associated with a single long branch, possessing mutations associated with increased bile tolerance, suggesting that the first H58 organism was generated during chronic carriage. The subsequent use of fluoroquinolones led to several independent mutations in gyrA. The ability of H58 to acquire and maintain AMR genes continues to pose a threat, as extensively drug-resistant (XDR; MDR plus resistance to ciprofloxacin and third generation cephalosporins) variants, have emerged recently in this lineage. Understanding where and how H58 S. Typhi originated and became successful is key to understand how AMR drives successful lineages of bacterial pathogens. Additionally, these data can inform optimal targeting of typhoid conjugate vaccines (TCVs) for reducing the potential for emergence and the impact of new drug-resistant variants. Emphasis should also be placed upon the prospective identification and treatment of chronic carriers to prevent the emergence of new drug resistant variants with the ability to spread efficiently.
Topics: Salmonella typhi; Typhoid Fever; Phylogeny; Humans; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Haplotypes; Mutation; Genome, Bacterial
PubMed: 38942806
DOI: 10.1038/s42003-024-06451-8 -
Open Veterinary Journal May 2024infections are considered the most common foodborne pathogens responsible for zoonotic infections and food poisoning in humans and animal species such as birds....
BACKGROUND
infections are considered the most common foodborne pathogens responsible for zoonotic infections and food poisoning in humans and animal species such as birds. Antimicrobial resistance is considered a global anxiety because it causes human public health repercussions, as well as leads to an increase in animal morbidity and death.
AIM
The aims of this study are the isolation and identification of , as well as to investigate the antimicrobial susceptibility test (AST) and the molecular characteristics using polymerase chain reaction (PCR) and sequences for isolates from chicken products (eggs, livers, and minced meat) and human in the Wasit Governorate of Iraq.
METHODS
A total of 300 samples (150 chicken product samples including eggs, livers, and minced meat, and 150 human fecal samples) were collected from the Wasit governorate of Iraq from January to December 2022. The bacterial isolation was done according to recommendations of ISO 6579 standard and the Global Foodborne Infections Network laboratory protocol. Serotyping test and AST were done by using 19 antibiotic agents according to the recommendations of the Clinical and Laboratory Standards Institute, 2022 by using disc diffusion susceptibility test and Vitik 2 test. Finally, the suspected isolates were confirmed using the conventional PCR method and sequencing for a unique gene.
RESULTS
The results showed that the isolation percentage of in chicken products was 8.66% (12% eggs, 6% livers, and 8% minced meat), while in humans it was 4.6%. Also, showed 100% of in humans. While, in chicken eggs , and were 50%, 33.33%, and 16.66%, respectively. Also, showed 100% of in both livers and minced meat. The AST in human isolates showed resistance to Ampicillin, Cefotaxime, Ceftazidime, Cefepime, Amikacin, Gentamicin, Ciprofloxacin, Norfloxacin, and Ceftriaxone, while no resistance to Amoxicillin, Pipracillin, Ertapenem, Imipenem, Meropenem, Fosfomycin, Nitrofurantoin, Trimethoprim, Azithromycin, and Tetracycline. In chicken products, isolates were resistant with different percentages to Amikacin, Gentamicin, Tetracycline, Ciprofloxacin, Norfloxacin, Nitrofurantoin, Ampicillin, Cefotaxime, Ceftazidime, Cefepime, and Trimethoprim; while no resistance to Amoxicillin, Pipracillin, Ertapenem, Imipenem, Meropenem, Fosfomycin, Azithromycin, and Ceftriaxone. Sequencing by using gene was done for four PCR products.
CONCLUSION
This study showed the presence of genetic mutations for which led to variations in the molecular characteristics, and antimicrobial drug resistance of isolated from chicken products and humans.
Topics: Animals; Salmonella enterica; Humans; Chickens; Iraq; Anti-Bacterial Agents; Drug Resistance, Bacterial; Microbial Sensitivity Tests; Meat; Feces; Poultry Products; Salmonella Infections
PubMed: 38938436
DOI: 10.5455/OVJ.2024.v14.i5.5 -
Animal Bioscience Jun 2024Somatostatin (SS) plays important regulatory roles in animal growth and reproduction by affecting the synthesis and secretion of growth hormone (GH). However, the...
OBJECTIVE
Somatostatin (SS) plays important regulatory roles in animal growth and reproduction by affecting the synthesis and secretion of growth hormone (GH). However, the mechanism by which SS regulates growth and development in goats is still unclear.
METHODS
In this study, we randomly selected eight 7-month-old Dazu black goats (DBGs) of similar body weight and equally assigned four bucks as the immunised and negative control groups. The immunised group received the Salmonella typhi attenuated vaccine CSO22 (ptCS/2SS-asd) orally, whilst the negative control group received the empty vector vaccine CSO22 (pVAX-asd) orally.
RESULTS
The SS concentration in the serum of goats in the immunised group was significantly lower than that in the negative control group, and the daily gain was significantly higher (p < 0.05). SS-14 DNA vaccine immunisation resulted in significantly higher concentrations of growth-related hormones such as GH-releasing hormone and IGF-1 in the serum of goats (p < 0.05). RNA-seq analysis of hypothalamus of oral SS-14 DNA vaccine and negative control DBGs identified 31 differentially expressed genes (DEGs). Pituitary gland identified 164 DEGs. A total of 246 DEGs were detected in the liver by RNA-seq. Gene ontology (GO) of DEGs was enriched in mitochondrial envelope, extracellular region, receptor binding and cell proliferation. The biological metabolic pathways associated with DEGs were explored by Kyoto Encyclopedia of Genes and Genomes analysis. DEGs were associated with metabolic pathways, oxidative phosphorylation, vitamin digestion and absorption and galactose metabolism. These candidate genes (e.g. DGKK, CYTB, DUSP1 and LRAT) may provide references for exploring the molecular mechanisms by which SS promotes growth and development.
CONCLUSION
Overall, these results demonstrated that the SS DNA vaccine enhanced the growth of DBGs by altering growth-related hormone concentrations and regulating the expression of growth-related genes in the hypothalamic-pituitary-liver axis.
PubMed: 38938026
DOI: 10.5713/ab.24.0121 -
Vaccines Jun 2024Serovar Typhi Ty21a (Ty21a) is the only licensed oral vaccine against typhoid fever. Due to its excellent safety profile, it has been used as a promising vector strain...
Serovar Typhi Ty21a (Ty21a) is the only licensed oral vaccine against typhoid fever. Due to its excellent safety profile, it has been used as a promising vector strain for the expression of heterologous antigens for mucosal immunization. As the efficacy of any bacterial live vector vaccine correlates with its ability to express and present sufficient antigen, the genes for antigen expression are traditionally located on plasmids with antibiotic resistance genes for stabilization. However, for use in humans, antibiotic selection of plasmids is not applicable, leading to segregational loss of the antigen-producing plasmid. Therefore, we developed an oral Ty21a-based vaccine platform technology, the JMU-SalVac-system (Julius-Maximilians-Universität Würzburg) in which the antigen delivery plasmids (pSalVac-plasmid-series) are stabilized by a Δ/-based balanced-lethal system (BLS). The system is made up of the chromosomal knockout of the essential tyrosyl-tRNA-synthetase gene () and the in trans complementation of on the pSalVac-plasmid. Further novel functional features of the pSalVac-plasmids are the presence of two different expression cassettes for the expression of protein antigens. In this study, we present the construction of vaccine strains with BLS plasmids for antigen expression. The expression of cytosolic and secreted mRFP and cholera toxin subunit B (CTB) proteins as model antigens is used to demonstrate the versatility of the approach. As proof of concept, we show the induction of previously described in vivo inducible promoters cloned into pSalVac-plasmids during infection of primary macrophages and demonstrate the expression of model vaccine antigens in these relevant human target cells. Therefore, antigen delivery strains developed with the JMU-SalVac technology are promising, safe and stable vaccine strains to be used against mucosal infections in humans.
PubMed: 38932416
DOI: 10.3390/vaccines12060687 -
The American Journal of Tropical... Jun 2024Iliopsoas abscess is an infrequent condition characterized by the collection of pus in the iliopsoas compartment. The prevalence of the disease has been increasing in...
Iliopsoas abscess is an infrequent condition characterized by the collection of pus in the iliopsoas compartment. The prevalence of the disease has been increasing in recent years with the emergence of various comorbidities and risk factors. The availability of newer imaging modalities has also improved the detection of new cases. Salmonellosis is an uncommon etiology in iliopsoas abscess and sacroiliitis. Most cases reported in the literature are associated with Staphylococcus aureus, Streptococci species, and Escherichia coli. Diabetes, hematological malignancies, HIV, and other immunocompromised states are important comorbidities/risk factors for iliopsoas abscess. We report a case of an 18-year-old male who presented with a history of fever and right hip pain for 10 days. Radioimaging revealed right sacroiliitis and iliopsoas abscess. Blood culture revealed pan-sensitive Salmonella typhi. After the prolonged course of antibiotics (intravenous ceftriaxone followed by oral levofloxacin), the patient improved with no further relapse in symptoms. Salmonella typhi should be an important differential of iliopsoas abscess in endemic regions after ruling out the common etiology such as S. aureus and Mycobacterium tuberculosis.
PubMed: 38917785
DOI: 10.4269/ajtmh.24-0045 -
PloS One 2024Typhoid fever, caused by Salmonella enterica serovar typhi, presents a substantial global health threat, particularly in regions with limited healthcare infrastructure....
Typhoid fever, caused by Salmonella enterica serovar typhi, presents a substantial global health threat, particularly in regions with limited healthcare infrastructure. The rise of multidrug-resistant strains of S. typhi exacerbates this challenge, severely compromising conventional treatment efficacy due to over activity of efflux pumps. In our study, a comprehensive exploration of two fundamental aspects to combat MDR in S. typhi is carried out; i.e. employing advanced bioinformatics analyses and AlphaFold AI, We successfully identified and characterised a putative homologue, ABC-TPA, reminiscent of the P-glycoprotein (P-gp) known for its role in multidrug resistance in diverse pathogens. This discovery provides a critical foundation for understanding the potential mechanisms driving antibiotic resistance in S. typhi. Furthermore, employing computational methodologies, We meticulously assessed the potential of lignans, specifically Schisandrin A, B, and C, as promising Efflux Pump Inhibitors (EPIs) against the identified P-gp homologue in S. typhi. Noteworthy findings revealed robust binding interactions of Schisandrin A and B with the target protein, indicating substantial inhibitory capabilities. In contrast, Schisandrin C exhibited instability, showing varied effectiveness among the evaluated lignans. Pharmacokinetics and toxicity predictions underscored the favourable attributes of Schisandrin A, including prolonged action duration. Furthermore, high systemic stability and demanished toxicity profile of SA and SB present their therapeutic efficacy against MDR. This comprehensive investigation not only elucidates potential therapeutic strategies against MDR strains of S. typhi but also highlights the relevance of computational approaches in identifying and evaluating promising candidates. These findings lay a robust foundation for future empirical studies to address the formidable challenges antibiotic resistance poses in this clinically significant infectious diseases.
Topics: Salmonella typhi; Drug Resistance, Multiple, Bacterial; Lignans; Anti-Bacterial Agents; Bacterial Proteins; Humans; Microbial Sensitivity Tests; Computational Biology
PubMed: 38917154
DOI: 10.1371/journal.pone.0303285 -
PLoS Neglected Tropical Diseases Jun 2024Salmonella enterica serotype Typhi (Salmonella Typhi) causes severe and occasionally life-threatening disease, transmitted through contaminated food and water. Humans...
BACKGROUND
Salmonella enterica serotype Typhi (Salmonella Typhi) causes severe and occasionally life-threatening disease, transmitted through contaminated food and water. Humans are the only reservoir, inadequate water, sanitation, and hygiene infrastructure increases risk of typhoid. High-quality data to assess spatial and temporal relationships in disease dynamics are scarce.
METHODS
We analyzed data from a prospective cohort conducted in an urban slum area of Dhaka City, Bangladesh. Passive surveillance at study centers identified typhoid cases by microbiological culture. Each incident case (index case) was matched to two randomly selected index controls, and we measured typhoid incidence in the population residing in a geographically defined region surrounding each case and control. Spatial clustering was evaluated by comparing the typhoid incidence in residents of geometric rings of increasing radii surrounding the index cases and controls over 28 days. Temporal clustering was evaluated by separately measuring incidence in the first and second 14-day periods following selection. Incidence rate ratios (IRRs) were calculated using Poisson regression models.
RESULTS
We evaluated 141 typhoid index cases. The overall typhoid incidence was 0.44 per 100,000 person-days (PDs) (95% CI: 0.40, 0.49). In the 28 days following selection, the highest typhoid incidence (1.2 per 100,000 PDs [95% CI: 0.8, 1.6]) was in the innermost cluster surrounding index cases. The IRR in this innermost cluster was 4.9 (95% CI: 2.4, 10.3) relative to the innermost control clusters. Neither typhoid incidence rates nor relative IRR between index case and control populations showed substantive differences in the first and second 14-day periods after selection.
CONCLUSION
In the absence of routine immunization programs, geographic clustering of typhoid cases suggests a higher intensity of typhoid risk in the population immediately surrounding identified cases. Further studies are needed to understand spatial and temporal trends and to evaluate the effectiveness of targeted vaccination in disrupting typhoid transmission.
PubMed: 38913735
DOI: 10.1371/journal.pntd.0012273