A novel phospholipase A2 is a core component of the typhoid toxin genetic islet.

S. Typhi, the cause of typhoid fever, is a bacterial pathogen of substantial global importance. Typhoid toxin is a secreted AB-type toxin that is a key S. Typhi virulence factor encoded within a 5-gene genetic islet. Four genes in this islet have well-defined roles in typhoid toxin biology, however the function of the fifth gene is unknown. Here, we investigate the function of this gene, which we name ttaP. We show that ttaP is co-transcribed with the typhoid toxin subunit cdtB, and we perform genomic analyses that indicate that TtaP is very highly conserved in typhoid toxin islets found in diverse salmonellae. We show that TtaP is a distant homolog of group XIV secreted phospholipase A2 (PLA2) enzymes, and experimentally demonstrate that TtaP is a bona fide PLA2. Sequence and structural analyses indicate that TtaP differs substantially from characterized PLA2s, and thus represents a novel class of PLA2. Secretion assays revealed that TtaP is neither co-secreted with typhoid toxin, nor is it required for toxin secretion. Although TtaP is a phospholipase that remains associated with the S. Typhi cell, assays that probed for altered cell envelope integrity failed to identify any differences between wild-type S. Typhi and a ttaP deletion strain. Collectively, this study identifies a biochemical activity for the lone uncharacterized typhoid toxin islet gene and lays the groundwork for exploring how this gene factors into S. Typhi pathogenesis. This study further identifies a novel class of PLA2, enzymes that have a wide range of industrial applications.

Changes in monocyte subsets in volunteers who received an oral wild-type Salmonella Typhi challenge and reached typhoid diagnosis criteria.

An oral Controlled Human Infection Model (CHIM) with wild-type S. Typhi was re-established allowing us to explore the development of immunity. In this model, ~55% of volunteers who received the challenge reached typhoid diagnosis criteria (TD), while ~45% did not (NoTD). Intestinal macrophages are one of the first lines of defense against enteric pathogens. Most organs have self-renewing macrophages derived from tissue-resident progenitor cells seeded during the embryonic stage; however, the gut lacks these progenitors, and all intestinal macrophages are derived from circulating monocytes. After infecting gut-associated lymphoid tissues underlying microfold (M) cells, S. Typhi causes a primary bacteremia seeding organs of the reticuloendothelial system. Following days of incubation, a second bacteremia and clinical disease ensue. S. Typhi likely interacts with circulating monocytes or their progenitors in the bone marrow. We assessed changes in circulating monocytes after CHIM. The timepoints studied included 0 hours (pre-challenge) and days 1, 2, 4, 7, 9, 14, 21 and 28 after challenge. TD participants provided extra samples at the time of typhoid diagnosis, and 48-96 hours later (referred as ToD). We report changes in Classical Monocytes -CM-, Intermediate Monocytes -IM- and Non-classical Monocytes -NCM-. Changes in monocyte activation markers were identified only in TD participants and during ToD. CM and IM upregulated molecules related to interaction with bacterial antigens (TLR4, TLR5, CD36 and CD206). Of importance, CM and IM showed enhanced binding of S. Typhi. Upregulation of inflammatory molecules like TNF-α were detected, but mechanisms involved in limiting inflammation were also activated (CD163 and CD354 downregulation). CM upregulated molecules to interact/modulate cells of the adaptive immunity, including T cells (HLA-DR, CD274 and CD86) and B cells (CD257). Both CM and IM showed potential to migrate to the gut as integrin α4ß7 was upregulated. Unsupervised analysis revealed 7 dynamic cell clusters. Five of these belonged to CM showing that this is the main population activated during ToD. Overall, we provide new insights into the changes that diverse circulating monocyte subsets undergo after typhoid diagnosis, which might be important to control this disease since these cells will ultimately become intestinal macrophages once they reach the gut.

Genetic heterogeneity in the Salmonella Typhi Vi capsule locus: a population genomic study from Fiji.

Typhoid fever is endemic in many parts of the world and remains a major public health concern in tropical and sub-tropical developing nations, including Fiji. To address high rates of typhoid fever, the Northern Division of Fiji implemented a mass vaccination with typhoid conjugate vaccine (Vi-polysaccharide conjugated to tetanus toxoid) as a public health control measure in 2023. In this study we define the genomic epidemiology of Salmonella Typhi in the Northern Division prior to island-wide vaccination, sequencing 85% (n=419) of the total cases from the Northern and Central Divisions of Fiji that occurred in the period 2017-2019. We found elevated rates of nucleotide polymorphisms in the tviD and tviE genes (responsible for Vi-polysaccharide synthesis) relative to core genome levels within the Fiji endemic S. Typhi genotype 4.2. Expansion of these findings within a globally representative database of 12 382 S. Typhi (86 genotyphi clusters) showed evidence of convergent evolution of the same tviE mutations across the S. Typhi population, indicating that tvi selection has occurred both independently and globally. The functional impact of tvi mutations on the Vi-capsular structure and other phenotypic characteristics are not fully elucidated, yet commonly occurring tviE polymorphisms localize adjacent to predicted active site residues when overlayed against the predicted TviE protein structure. Given the central role of the Vi-polysaccharide in S. Typhi biology and vaccination, further integrated epidemiological, genomic and phenotypic surveillance is required to determine the spread and functional implications of these mutations.

The use of controlled human infection models to identify correlates of protection for invasive Salmonella vaccines.

Controlled human infection model (CHIM) studies, which involve deliberate exposure of healthy human volunteers to an infectious agent, are recognised as important tools to advance vaccine development. These studies not only facilitate estimates of vaccine efficacy, but also offer an experimental approach to study disease pathogenesis and profile vaccine immunogenicity in a controlled environment, allowing correlation with clinical outcomes. Consequently, the data from CHIMs can be used to identify immunological correlates of protection (CoP), which can help accelerate vaccine development. In the case of invasive Salmonella infections, vaccination offers a potential instrument to prevent disease. Invasive Salmonella disease, caused by the enteric fever pathogens Salmonella enterica serovar Typhi (S. Typhi) and S. Paratyphi A, B and C, and nontyphoidal Salmonella (iNTS), remains a significant cause of mortality and morbidity in low- and middle-income countries, resulting in over 200,000 deaths and the loss of 15 million DALYs annually. CHIM studies have contributed to the understanding of S. Typhi infection and provided invaluable insight into the development of vaccines and CoP following vaccination against S. Typhi. However, CoP are less well understood for S. Paratyphi A and iNTS. This brief review focuses on the contribution of vaccine-CHIM trials to our understanding of the immune mechanisms associated with protection following vaccines against invasive Salmonella pathogens, particularly in relation to CoP.

Case report: Thoracic vertebral abscess caused by Salmonella via diagnosed next-generation sequencing.

The genus Salmonella consists of Gram-negative bacteria with various serotypes. It commonly causes bacterial infections that affect the intestines. Infection can occur in humans and animals through the ingestion of contaminated food or water, or through contact with infected animals or environments. Complications commonly include intestinal hemorrhage and perforation, though vertebral osteomyelitis is rarely observed. Therefore, in patients with spinal cord abscesses, The genus Salmonella is typically not considered a likely pathogen, especially in the absence of typical symptoms. In this case, the limited information provided by traditional cultivation methods, particularly under the influence of antibiotics. However, next-generation sequencing (NGS) unexpectedly detected Salmonella, which assisted in formulating the final treatment plan. This underscores the role and clinical value of NGS in pathogen identification.

Azithromycin-resistant mph(A)-positive Salmonella enterica serovar Typhi in the United States.

OBJECTIVES: . The United States Centers for Disease Control and Prevention (CDC) conducts active surveillance for typhoid fever cases caused by Salmonella enterica serovar Typhi (Typhi). Here we describe the characteristics of the first two cases of mph(A)-positive azithromycin-resistant Typhi identified through US surveillance. METHODS: . Isolates were submitted to public health laboratories, sequenced, and screened for antimicrobial resistance determinants and plasmids, as part of CDC PulseNet's routine genomic surveillance. Antimicrobial susceptibility testing and long-read sequencing were also performed. Basic case information (age, sex, travel, outcome) was collected through routine questionnaires; additional epidemiological data was requested through follow-up patient interviews. RESULTS: . The patients are related and both reported travel to India (overlapping travel dates) before illness onset. Both Typhi genomes belong to the GenoTyphi lineage 4.3.1.1 and carry the azithromycin-resistance gene mph(A) on a PTU-FE (IncFIA/FIB/FII) plasmid. These strains differ genetically from mph(A)-positive Typhi genomes recently reported from Pakistan, suggesting independent emergence of azithromycin resistance in India. CONCLUSIONS: . Cases of typhoid fever caused by Typhi strains resistant to all available oral treatment options are cause for concern and support the need for vaccination of travelers to Typhi endemic regions. US genomic surveillance serves as an important global sentinel for detection of strains with known and emerging antimicrobial resistance profiles, including strains from areas where routine surveillance is not conducted.

Exploring the antimicrobial efficacy of Manuka honey against multidrug-resistant and extensively drug-resistant Salmonella Typhi causing septicemia in Pakistan.

Aim: To determine the efficacy of manuka honey against multidrug-resistant (MDR) and extensively drug-resistant (XDR) clinical strains of Salmonella Typhi. Materials & methods: Clinical isolates were processed using the Bactec blood culture system, identification and antibiogram by Vitek 2 and antibiotic resistance genes through polymerase chain reaction (PCR). Microbroth dilution assays evaluated the antibacterial activity of manuka honey. Results: MDR and XDR-S. Typhi was susceptible to azithromycin. These strains carried the H58, gyrA, gyrB, blaCTX-M-15 , and blaTEM-1 genes. At 100% honey, the zone of inhibition for MDR (15-23 mm) and XDR (15-24 mm) strains. 18/50 MDR and 14/50 XDR strains inhibited at 3.125 v/v% killed at 6.25 v/v% concentration respectively. Conclusion: Manuka honey could be an alternative option for treating S. Typhi infections.

Typhoid fever is a life-threatening bacterial infection caused by the Salmonella Typhi. These bacteria are transmitted through contaminated water and food and cause fever, abdominal pain, headache, vomiting, and diarrhea mainly in children under 5. There are around 9 million people get infected with S. Typhi, with an increased death of 1,10,000 annually. Bees that collect nectar from the blossoms of the Manuka tree in Australia and New Zealand produce a type of honey known as manuka honey. This honey is famous for its antibacterial activity, and potential health benefits. Therefore, we aimed to determine its antibacterial activity against S. Typhi. Our finding shows that the commonly available antibiotics did not kill S. Typhi because their DNA was drug-resistant. After applying the manuka honey, these bacteria were killed and given a clear zone ranging from 15­24mm on the agar plate. Further analysis revealed that at low concentrations of manuka honey, 3.1% and 6.25%, most of the S. Typhi stopped growing and killed, respectively. This study suggested that manuka honey, which is affordable and readily available, could be used as a treatment option to treat infections produced by these harmful bacteria after further analysis.

Exploring the Antimicrobial Resistance Profile of Salmonella typhi and Its Clinical Burden.

Background: Typhoid fever caused by Salmonella enterica serovar Typhi (S. typhi) continues to pose a significant risk to public health in developing countries, including Pakistan. This study investigated the epidemiological factors linked to suspected and confirmed S. typhi infections in Peshawar's hospital population. Methodology: A total of 5735 blood samples of patients with suspected enteric fever were collected from September 2022 to November 2023. S. typhi infection was confirmed using microbiological culture of blood samples, biochemical-based tests, and DNA-sequencing methods. Drug sensitivity testing on cultures was conducted as per the CLSI guidelines. Chi-square tests were used to analyze the clinical and epidemiologic characteristics of 5735 samples stratified by S. typhi infection status, and risk factors were assessed by applying logistic regression models to estimate odds ratios (ORs). Results: The number of confirmed typhoid fever cases in this hospital-based study population was 691 (/5735, 12.0%), more prevalent in males (447/3235 13.8%) and children (0-11 years) (429/2747, 15.6%). Compared to children, the risk of S. typhi infection was lower in adolescence (adjusted OR = 0.52; 95% CI: 0.42-0.66), adulthood (19-59 years; aOR = 0.30; 95% CI: 0.25-0.38), and older adulthood (aOR = 0.08; 95% CI: 0.04-0.18) (p < 0.001). Compared to males, the risk of S. typhi infection was lower in females (aOR = 0.67; 95% CI = 0.56-0.80; p = 0.002). Living in a rural residence (compared to urban) was associated with a higher risk of infection (aOR = 1.38; 95% CI: 1.16-1.63; p = 0.001), while access to a groundwater source (compared to municipal water supply) led to a lower risk (aOR = 0.56; 95% CI: 0.43-0.73; p = 0.002). Vaccination demonstrated a robust protective effect (aOR = 0.069; 95% CI = 0.04-0.11, p = 0.002). For those with typhoid infections, clinical biomarker analysis revealed the presence of leucopenia (65/691, 9.4%), thrombocytopenia (130/691, 18.8%), and elevated alanine aminotransferase (ALT) (402/691, 58.2%) and C-reactive protein (CRP) (690/691, 99.9%) levels. Worryingly, among the positive S. typhi isolates, there was a high prevalence of drug resistance (653/691), including multidrug-resistant (MDR 82/691, 11.9%) and extensively drug-resistant types (XDR, 571/691, 82.6%). Conclusions: This study highlights the importance of age, sex, locality, water source, and vaccination status in shaping the epidemiological landscape of S. typhi in the Peshawar district. It implies that expanding vaccination coverage to the broader population of Khyber Pakhtunkhwa province, particularly in the district of Peshawar, would be beneficial.

TolC facilitates the intracellular survival and immunomodulation of Salmonella Typhi in human host cells.

Salmonella enterica serovar Typhi (S. Typhi) causes typhoid fever, a systemic infection that affects millions of people worldwide. S. Typhi can invade and survive within host cells, such as intestinal epithelial cells and macrophages, by modulating their immune responses. However, the immunomodulatory capability of S. Typhi in relation to TolC-facilitated efflux pump function remains unclear. The role of TolC, an outer membrane protein that facilitates efflux pump function, in the invasion and immunomodulation of S. Typhi, was studied in human intestinal epithelial cells and macrophages. The tolC deletion mutant of S. Typhi was compared with the wild-type and its complemented strain in terms of their ability to invade epithelial cells, survive and induce cytotoxicity in macrophages, and elicit proinflammatory cytokine production in macrophages. The tolC mutant, which has a defective outer membrane, was impaired in invading epithelial cells compared to the wild-type strain, but the intracellular presence of the tolC mutant exhibited greater cytotoxicity and induced higher levels of proinflammatory cytokines (IL-1ß and IL-8) in macrophages compared to the wild-type strain. These effects were reversed by complementing the tolC mutant with a functional tolC gene. Our results suggest that TolC plays a role in S. Typhi to efficiently invade epithelial cells and suppress host immune responses during infection. TolC may be a potential target for the development of novel therapeutics against typhoid fever.

Transcriptional regulator MarT negatively regulates MarT-regulated motility gene I, a new gene involved in invasion and virulence of Salmonella enterica.

The speciation of Salmonella occurred by acquisition of genomic islands from other bacterial species and continued to diverge into subspecies and serovars with diferent range of host. S. enterica serovar Typhimurium (STM) is a generalist pathogen infecting hosts that include birds, mice, and humans, whilst S. enterica serovar Typhi (STY) is a restricted-host pathogen, infecting only humans. Despite their ranges of hosts, STM and STY possess 97-98% identity. Gain of genes by horizontal transference and loss of genes by mutations, are believed essential for differentiation of Salmonella. Salmonella pathogenicity island 3 (SPI-3) is an example combining these two processes. SPI-3 encodes misL and marT, among other genes. In STM, misL is required for gut colonization. Furthermore, protein MarT, positively regulates expression of misL by binding to misL-promoter. On the other hand, in SPI-3 of STY, marT and misL are pseudogenes. Interestingly, the gene t3766 (gene involved in resistance to H2O2) is present only in STY and is negatively regulated when marT STM is heterologously expressed in STY. Based on the view that MarT might regulate genes implicated in virulence, this work searched for new genes regulated by MarT. In silico searches for possible MarT target genes were performed, and 4 genes were selected for further analysis as they contained at least 2 copies of the consensus MarT-binding sequence in their promoters. Mutating marT in STM or heterologously expressing marT STM in STY confirmed that MarT negatively regulates ORF STY1408 or STM14_2003, its homologue in STM. STY1408 encodes for a putative protein with homology to methyl accepting chemotaxis proteins, which participate in chemotaxis and motility. Therefore, STY1408 was named mrmI (MarT-regulated motility gene I). Motility assays confirmed that the product of mrmI modulates motility. In addition, in vitro infection of cells with STM and STY mutants in mrmI reduces association with cells at 1, 3 and 24 h post-infection. Oral infection of mice showed that a mrmI null mutant was defective in producing systemic disease. Therefore, we conclude that MarT regulated mrmI, is involved in virulence of Salmonella. While pseudogenization of marT might modulate the fitness of narrow host range STY.

Flea-Borne Rickettsioses and Scrub Typhus in Patients with Suspected Arbovirus Infection in Bangkok, Thailand.

Background: In urban Thailand, arboviral infections dominate diagnoses of acute undifferentiated fevers (AUFs) owing to their well-defined epidemiology and characteristic clinical presentations. However, rickettsial diseases, also endemic in this setting, remain under-recognized owing to challenges in early detection. Objective: This study aimed to identify potential rickettsial infections among patients with AUF in Bangkok and vicinity utilizing leftover nucleic acid extracted from serum samples from patients initially suspected of but negative for arbovirus infections. Materials and Methods: A total of 609 nucleic acid samples were screened for rickettsial bacteria using real-time PCR, targeting the 17-kDa common antigen gene of Rickettsia spp. and the 47-kDa gene of Orientia tsutsugamushi. Results: Nine samples were positive for Rickettsia spp. and two were positive for O. tsutsugamushi. DNA sequence and phylogenetic analyses based on partial 17-kDa antigen and citrate synthase (gltA) genes identified the Rickettsia-positive samples as R. typhi in eight cases and R. felis in one case. Analysis of the 56-kDa type-specific antigen gene identified the two O. tsutsugamushi isolates as Gilliam-related genotypes. Although rickettsial diseases typically present with mild symptoms, two patients with R. typhi infection (murine typhus) developed respiratory distress syndrome, highlighting the potential for rare but serious complications. Conclusion: This study underscores the critical importance of differential diagnosis and prompt, effective intervention to prevent complications in suspected cases.

Evolving Epidemiology and Antibiotic Resistance in Enteric Fever: A Comprehensive Review.

Enteric fever, predominantly caused by Salmonella enterica serovar Typhi and Salmonella enterica serovar Paratyphi, remains a significant global health challenge. This comprehensive review examines the evolving epidemiology and antibiotic resistance associated with enteric fever. We provide an overview of the disease's definition and historical context, highlighting the substantial impact of antibiotic resistance on treatment efficacy. The review details the global burden, incidence trends, and risk factors of enteric fever while elucidating the pathogenesis and clinical manifestations of the disease. A critical analysis of antibiotic resistance mechanisms reveals the alarming rise of multi-drug resistant (MDR) and extensively drug-resistant (XDR) strains, complicating treatment regimens and underscoring the need for novel therapeutic strategies. Current treatment protocols, the role of empirical therapy, and the rational use of antibiotics are discussed in depth. Additionally, we explore prevention and control strategies, emphasizing the importance of vaccination programs, sanitation improvements, and effective public health interventions. The review concludes with recommendations for future actions, including enhanced surveillance, research and development of new antibiotics, expansion of vaccination efforts, and improved public health infrastructure. The findings highlight the necessity for updated clinical guidelines and sustained global efforts to address the challenges of enteric fever and its evolving antibiotic resistance patterns. Through coordinated action and continued innovation, it is possible to mitigate the impact of this enduring public health threat.

Salmonella Typhi genotypic diversity, cluster identification and antimicrobial resistance determinants in Mukuru settlement, Nairobi Kenya.

BACKGROUND: Understanding the source of typhoid infections and the genetic relatedness of Salmonella Typhi (S. Typhi) by cluster identification in endemic settings is critical for establishing coordinated public health responses for typhoid fever management. This study investigated the genotypic diversity, antibiotic resistance mechanisms, and clustering of 35 S.Typhi strains isolated from cases and carriers in the Mukuru Informal Settlement. METHODS: We studied 35 S.Typhi isolates, including 32 from cases and 3 from carriers, from study participants in the informal settlement of Mukuru, Nairobi, Kenya. Genomic DNA was extracted, and whole-genome sequencing (WGS) was performed to determine the phylogenetic relatedness of strains and detect antimicrobial resistance determinants (AMR). WGS data were analyzed using bioinformatics tools available at the Center for Genomic Epidemiology and Pathogenwatch platforms. RESULTS: Genotype 4.3.1.2 EA3 was found to be dominant at 46% (16/35), followed by 4.3.1.2 EA2 at 28% (10/35), and 4.3.1.1 EA1 at 27% (9/35). A comparison of the isolates with global strains from Pathogenwatch identified close clustering with strains from Uganda, Tanzania, Rwanda, and India. Three isolates (9%) distributed in each cluster were isolated from carriers. All genotype 4.3.1.2 EA3 isolates were genotypically multidrug-resistant to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole. Single mutations in the quinolone resistance-determining region were identified in the gyrA (S83Y) and gyrB (S464F) genes. All isolates associated with multidrug resistance showed the presence of the IncQ1 plasmid with the following genes: blaTEM-1B, catA1, sul1, sul2, and dfrA7. CONCLUSION: The close phylogenetic relatedness between antimicrobial-resistant case isolates and carriage isolates indicates that typhoid carriage is a possible source of infection in the community. Comparative analysis with global isolates revealed that the Kenyan isolates share common lineages with strains from neighboring East African countries and India, suggesting regional dissemination of specific MDR clones. AMR was a major feature of the isolates. Surveillance and testing for antimicrobial susceptibility should inform options for the management of cases.

Mobile genetic elements define the non-random structure of the Salmonella enterica serovar Typhi pangenome.

Bacterial relatedness measured using select chromosomal loci forms the basis of public health genomic surveillance. While approximating vertical evolution through this approach has proven exceptionally valuable for understanding pathogen dynamics, it excludes a fundamental dimension of bacterial evolution-horizontal gene transfer. Incorporating the accessory genome is the logical remediation and has recently shown promise in expanding epidemiological resolution for enteric pathogens. Employing k-mer-based Jaccard index analysis, and a novel genome length distance metric, we computed pangenome (i.e., core and accessory) relatedness for the globally important pathogen Salmonella enterica serotype Typhi (Typhi), and graphically express both vertical (homology-by-descent) and horizontal (homology-by-admixture) evolutionary relationships in a reticulate network of over 2,200 U.S. Typhi genomes. This analysis revealed non-random structure in the Typhi pangenome that is driven predominantly by the gain and loss of mobile genetic elements, confirming and expanding upon known epidemiological patterns, revealing novel plasmid dynamics, and identifying avenues for further genomic epidemiological exploration. With an eye to public health application, this work adds important biological context to the rapidly improving ways of analyzing bacterial genetic data and demonstrates the value of the accessory genome to infer pathogen epidemiology and evolution.IMPORTANCEGiven bacterial evolution occurs in both vertical and horizontal dimensions, inclusion of both core and accessory genetic material (i.e., the pangenome) is a logical step toward a more thorough understanding of pathogen dynamics. With an eye to public, and indeed, global health relevance, we couple contemporary tools for genomic analysis with decades of research on mobile genetic elements to demonstrate the value of the pangenome, known and unknown, annotated, and hypothetical, for stratification of Salmonella enterica serovar Typhi (Typhi) populations. We confirm and expand upon what is known about Typhi epidemiology, plasmids, and antimicrobial resistance dynamics, and offer new avenues of exploration to further deduce Typhi ecology and evolution, and ultimately to reduce the incidence of human disease.

Extensively drug-resistant Salmonella typhi Infection in Adults; Experience from A Tertiary Care Hospital.

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 1st March to 10th 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.

Salmonella typhi and endocarditis: a systematic review of case reports.

Introduction: Salmonella typhi, a gram-negative bacterium responsible for typhoid fever, can infect the inner lining or valves of the heart and cause endocarditis. This systematic review aimed to report cases of S. typhi-associated endocarditis and its clinical features. Methods: This systematic review was reported as per the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) checklist. Only case reports and case series of endocarditis caused by S. typhi, irrespective of age, gender, and demographics, were considered eligible for inclusion. To identify relevant studies, a literature search was conducted using relevant keywords on PubMed, Google Scholar, and the Cochrane Library from inception to 31 December 2023. After selecting the studies, the relevant data were extracted and pooled in terms of frequencies and percentages. A quality assessment was performed using the Joanna Briggs Institute Critical Appraisal Checklist for Case Reports. Results: This review included seven case reports, comprising 22.2% female and 77.8% male patients. The mean age of patients was 27.9 + 12.0 years. Regarding past medical history, 33.3% (3/9) of patients had a previous cardiac pathology. Fever remained the most common complaint, occurring in 88.9% of cases. Transthoracic and transesophageal echocardiography were used to diagnose all cases, with 33.3% identifying vegetation on the mitral, aortic, and tricuspid valves. Ceftriaxone, with or without gentamycin, remained the choice of antibiotic for 88.9% of cases, and all patients responded to the offered treatment. Conclusion: S. typhi-associated endocarditis, though rare, presents unique challenges and requires timely diagnosis. This systematic review of seven cases highlights a predominantly male population affected, with a mean age in the third decade, suggesting a higher invasiveness than other causes. The findings from this study underscore the importance of early recognition and appropriate management, primarily with antibiotic therapy. Further research with larger cohorts is crucial to refine understanding and guide policymaking for this rare but life-threatening condition.

Synthesis of 2-Ethylhexyl 5-Bromothiophene-2-Carboxylates; Antibacterial Activities against Salmonella Typhi, Validation via Docking Studies, Pharmacokinetics, and Structural Features Determination through DFT.

A new class of thiophene-based molecules of 5-bromothiophene-2-carboxylic acid (1) have been synthesized in current research work. All analogs 4A-4G were synthesized with optimized conditions by coupling reactions of 2-ethylhexyl 5-bromothiophene-2-carboxylate (3) with various arylboronic acids. The results indicated that the majority of compounds showed promising effective in vitro antibacterial activity. Herein, 2-ethylhexyl-5-(p-tolyl)thiophene-2-carboxylate (4F), in particular among the synthesized analogs, showed outstanding antibacterial action (MIC value 3.125 mg/mL) against XDR Salmonella Typhi compared to ciprofloxacin and ceftriaxone. The intermolecular interaction was investigated by using a molecular docking study of thiophene derivatives 4A-4G against XDR S. Typhi. The values of the binding affinity of functionalized thiophene molecules and ciprofloxacin were compared against bacterial enzyme PDB ID: 5ztj. Therefore, 4F appears to be a promising antibacterial agent and showed the highest potential value. Density functional theory (DFT) calculations were executed to examine the electronic, structural, and spectroscopic features of the newly synthesized molecules 4A-4G.

Tracking the shift in enteric fever trends and evolving antibiotic sensitivity patterns.

Objective: This study aims to examine the frequency of Salmonella Paratyphi found in blood cultures and evaluate the antibiotic susceptibility pattern of Salmonella isolates to different antibiotics. Additionally, the study aims to assess the paradigm shift in the trend of enteric fever caused by Salmonella Typhi (S. Typhi) to Salmonella Paratyphi(S. Paratyphi) . Study Design: Retrospective study. Participant: The study enrolled patients aged 12 years and above diagnosed with enteric fever (positive blood culture) and admitted to Peelamedu Samanaidu Govindasamy Naidu (PSG) Hospital. Interventions: The study analyzed demographic and antibiotic susceptibility profiles of Salmonella isolates collected from 106 enteric fever patients in the hospital between 2010 and 2022. The susceptibility profiles of Salmonella isolates to multiple antibiotics were assessed. Results: There were 106 participants, and 95 (89.62%) of them had enteric fever linked to Salmonella Typhi, while only 11 (10.38%) had enteric fever linked to Salmonella Paratyphi A. From 2010 to 2022, the study discovered a general decline in the prevalence of enteric fever caused by Salmonella species. But between 2014 and 2022, the incidence of enteric fever linked to S. Typhi rapidly increased. Azithromycin (100% , n = 106) and ceftriaxone (99% , n = 105) were highly effective against the Salmonella isolates, whereas nalidixic acid was resisted by 3 isolates (4.72%, n = 3). Conclusion: The study observed a higher incidence of Salmonella Typhi in comparison to Paratyphi A and a greater susceptibility of males to enteric fever. Funding: None declared.

Evaluation of Antioxidant and Antimicrobial Activity of Ethanolic Extract of Medicinal Plants Baccaurea Ramiflora and Microcos Paniculata.

OBJECTIVE: The present study was undertaken to investigate the antioxidant and antimicrobial effect of ethanolic leaf extract of Baccaurea ramiflora and Microcos paniculata. METHODS: DPPH radical scavenging activity, Nitric oxide scavenging activity, Super oxide anion radical scavenging activity, Reducing power assay were used to assess antioxidant efficacy. Zone of Inhibition determination by Agar well diffusion assay was used to assess antimicrobial activity. RESULTS: The Baccaurea ramiflora and Microcos paniculata leaves extracted with different solvents such as petroleum ether, chloroform, ethanol and water among that in leaves ethanolic extract produce 10.78, 10.38 percentage yield respectively. Both the extracts subjected for phytochemical investigation revealed the presence of alkaloids, glycosides, tannins, saponins, proteins and flavonoids. Ethanolic extract of Baccaurea ramiflora showed maximum inhibition zone diameter was obtained in Salmonella typhi (Gram-negative bacteria) with diameter 29 mm and 25 mm respectively at 200mg/ml and 100mg/ml. Similarly, Ethanolic extract of Microcos paniculata showed minimum inhibition zone diameter compare to Baccaurea ramiflora was obtained in Salmonella typhi (Gram-negative bacteria) with diameter 23 mm and 19 mm respectively at 200mg/ml and 100mg/ml. Ethanolic extract of Baccaurea ramiflora showed maximum inhibition zone diameter was obtained in Aspergillus fumigates with diameter 25 mm and 22 mm respectively at 200mg/ml and 100mg/ml. Similarly, Ethanolic extract of Microcos paniculata showed minimum inhibition zone diameter compare to Baccaurea ramiflora was obtained in Aspergillus fumigates with diameter 21 mm and 19 mm respectively at 200mg/ml and 100mg/ml. CONCLUSION: The current findings point to Baccaurea ramiflora and Microcos paniculata antioxidant and antimicrobial properties. However future studies should be designed to isolate the active constituents responsible for the specified effect.

Seroprevalence of zoonotic pathogens in stray cats in an urban area of northeast Spain.

The feline population is extensive in urban areas worldwide, comprising stray and domestic cats. Cats, acting as reservoirs, can transmit various zoonotic organisms to humans, which can cause significant public health issues. We evaluated the seroprevalence of zoonotic pathogens in stray cats in an urban area of northeast Spain (the city of Zaragoza) to assess potential risks to human health. A total of 88 sampled cats (52 females and 36 males) underwent antibody evaluation using the indirect immunofluorescence technique. Seroprevalence rates were determined for IgG antibodies to Bartonella henselae (36.3%), Toxoplasma gondii (31.8%), Rickettsia felis (14.7%), Rickettsia typhi (9%), and Leishmania infantum (10.2%). Our results confirmed the presence in stray cats of antibodies against all those pathogens, indicating that they all circulate in the feline population in Zaragoza. Male cats exhibited a higher predisposition to T. gondii, whereas females showed an increased likelihood of contracting B. henselae. This difference may be attributed to distinct behaviors according to sex. Our findings underscore the importance of maintaining and intensifying surveillance coupled with preventive measures against zoonotic pathogens in cats. They highlight the need for comprehensive control strategies designed to mitigate public health risks associated with feline populations.