We report a severe case of a 25-year-old girl presented with complaints of weakness, diarrhoea, vomiting, pain in abdomen and hypotension at Infectious Diseases and Clinical Immunology Research Center. From history on 25 February till 29 February she was in India and on 1 march this problem started with watery diarrhoea followed by vomiting. She ate pizza with mushroom following which her condition worsened. Stool culture revealed salmonella nontyphi (nonthyphodal Salmonella)and this is leading cause for gastroenteritis, bacteremia and affects several other bodily system. Her condition deteriorated due to the development of ARDS (acute respiratory distress syndrome) and for this she was on mechanical ventilation. Vitec machine was performed, which identified Salmonella typhi murium. Our goal is to manage and treat this patient well by early diagnosis. She was given ceftriaxone, iv fluids and symptomatic treatment but due to resistance meropenem was started and the patient\'s condition improved. From serology there was no evidence of immunocompromised state so being a severe case of immunocompetent patient this case reflects the importance of timely diagnosis and management together with food safety practices in population. On follow up she was stable and discharged after 3 weeks. Future research studies need to be continued regarding newer strains, effective treatment strategies and diagnostics to prevent morbidity and mortality.

UNASSIGNED: 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) .
UNASSIGNED: Retrospective study.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: The study observed a higher incidence of Salmonella Typhi in comparison to Paratyphi A and a greater susceptibility of males to enteric fever.
UNASSIGNED: None declared.

UNASSIGNED: This study aimed to determine the epidemiology, clinical features, and complications of extensively drug-resistant Salmonella typhi (XDR S. typhi) infection in adults.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

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.

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.

Many bacterial pathogens, including the human exclusive pathogen Salmonella Typhi, express capsular polysaccharides as a crucial virulence factor. Here, through S. Typhi whole genome sequence analyses and functional studies, we found a list of single point mutations that make S. Typhi hypervirulent. We discovered a single point mutation in the Vi biosynthesis enzymes that control Vi polymerization or acetylation is enough to result in different capsule variants of S. Typhi. All variant strains are pathogenic, but the hyper Vi capsule variants are particularly hypervirulent, as demonstrated by the high morbidity and mortality rates observed in infected mice. The hypo Vi capsule variants have primarily been identified in Africa, whereas the hyper Vi capsule variants are distributed worldwide. Collectively, these studies increase awareness about the existence of different capsule variants of S. Typhi, establish a solid foundation for numerous future studies on S. Typhi capsule variants, and offer valuable insights into strategies to combat capsulated bacteria.

The causative agent of typhoid fever, Salmonella enterica serovar Typhi, is a human restricted pathogen. Human carriers, 90% of whom have gallstones in their gallbladder, continue to shed the pathogen after treatment. The genetic mechanisms involved in establishing the carrier state are poorly understood, but S. Typhi is thought to undergo specific genetic changes within the gallbladder as an adaptive mechanism. In the current study, we aimed to identify biofilm forming ability and the genetic differences in longitudinal clinical S. Typhi isolates from asymptomatic carriers with gallstones in Nairobi, Kenya. Whole genome sequences were analyzed from 22 S. Typhi isolates, 20 from stool and 2 from blood samples, all genotype 4.3.1 (H58). Nineteen strains were from four patients also diagnosed with gallstones, of whom, three had typhoid symptoms and continued to shed S. Typhi after treatment. All isolates had point mutations in the quinolone resistance determining region (QRDR) and only sub-lineage 4.3.1.2EA3 encoded multidrug resistance genes. There was no variation in antimicrobial resistance patterns among strains from the same patient/household. Non-multidrug resistant (MDR), isolates formed significantly stronger biofilms in vitro than the MDR isolates, p<0.001. A point mutation within the treB gene (treB A383T) was observed in strains isolated after clinical resolution from patients living in 75% of the households. Missense mutations in Vi capsular polysaccharide genes, tviE P263S was also observed in 18% of the isolates. This study provides insights into the role of typhoid carriage, biofilm formation, AMR genes and genetic variations in S. Typhi from asymptomatic carriers.

Primary aortoenteric fistulas (AEF) are rare. The majority of these are due to atherosclerotic aortic aneurysms. Mycotic aortic aneurysms leading to primary AEF are exceedingly uncommon. Here we report a rare case of primary AEF secondary to Salmonella-related mycotic aneurysm and discuss the diagnostic and therapeutic issues.

Introduction. Enteric fever is a significant health concern in endemic countries. While extensive research has been conducted to understand its presentation and outcomes in non-cancer patients, limited data exist on its impact on cancer patients. This descriptive study aims to investigate the clinical presentation and outcome in cancer patients. Methodology. This retrospective observational study analysed 90 adult cancer patients from a single centre in Pakistan from January 2017 to December 2022. Inclusion criteria involved documented blood culture infections with Salmonella typhi or paratyphi A, B, or C. We examined clinical presentation, laboratory parameters, antimicrobial resistance, complications, and outcomes. Additionally, we explored the effects of chemotherapy, comorbidities, type of malignancy, and patient age on complications and mortality. Results. Salmonella typhi was the most prevalent organism (72.2 %), followed by Salmonella paratyphi A (22.2 %) and B (5.5 %). Variably-resistant isolates constituted 51.5 %, multi-drug resistant (MDR) isolates accounted for 20 %, extensively drug-resistant (XDR) for 14.4 % and ESBL-producers for 15.5 %, of all enteric fever infections. Enteric fever-associated complications were observed in 21.1 % of cases. Chemotherapy in the preceding month did not affect mortality, nor did age, gender, or malignancy type. However, comorbidities were statistically significant for mortality (p-value 0.03). A total of 8.8 % of patients required ICU care, and the all-cause 30 day mortality rate was 13.3 % Conclusion. Enteric fever remains prevalent in our geographical region. Unlike non-typhoidal Salmonella (NTS), enteric fever does not behave differently in an immunocompromised population, including cancer patients.

BACKGROUND: Enteric fever is caused by Salmonella enterica serovars Typhi (S. Typhi) and Paratyphi A, B, and C. It continues to be a significant cause of morbidity and mortality worldwide. In highly endemic areas, children are disproportionately affected, and antimicrobial resistance reduces therapeutic options. It is estimated that 2-5% of enteric fever patients develop chronic asymptomatic infection. These carriers may act as reservoirs of infection; therefore, the prospective identification and treatment of carriers are critical for long-term disease control. We aimed to find the frequency of Salmonella Typhi carriers in patients undergoing cholecystectomy. We also compared the detection limit of culturing versus qPCR in detecting S. Typhi, performed a geospatial analysis of the carriers identified using this study, and evaluated the accuracy of anti-Vi and anti-YncE in identifying chronic typhoid carriage.
METHODS: We performed a cross-sectional study in two centers in Pakistan. Gallbladder specimens were subjected to quantitative PCR (qPCR) and serum samples were analyzed for IgG against YncE and Vi by ELISA. We also mapped the residential location of those with a positive qPCR result.
RESULTS: Out of 988 participants, 3.4% had qPCR-positive gallbladder samples (23 S. Typhi and 11 S. Paratyphi). Gallstones were more likely to be qPCR positive than bile and gallbladder tissue. Anti-Vi and YncE were significantly correlated (r = 0.78 p<0.0001) and elevated among carriers as compared to qPCR negative controls, except for anti-Vi response in Paratyphi A. But the discriminatory values of these antigens in identifying carriers from qPCR negative controls were low.
CONCLUSIONS: The high prevalence of typhoid carriers observed in this study suggests that further studies are required to gain information that will help in controlling future typhoid outbreaks in a superior manner than they are currently being managed.