Search Results (5)

Background and Objectives: In the undertaken study, proteomics alterations of blood-borne XDR S. Typhi isolated from Pakistan were investigated using mass spectrometry. Materials and Methods: MDR and XDR S. Typhi total protein lysates were fractionated, digested, and processed for nanoflow LC-LTQ-Orbitrap MS analysis. Results: Among the 1267 identified proteins, 37 were differentially regulated, of which 28 were up-regulated, and 9 were down-regulated in XDR S. Typhi as compared to MDR S. Typhi. Based on the functional annotation, proteins found up-regulated are involved mainly in metabolic pathways (ManA, FadB, DacC, GpmA, AphA, PfkB, TalA, FbaB, OtsA, 16504242), the biosynthesis of secondary metabolites (ManA, FadB, GlpB, GpmA, PfkB, TalA, FbaB, OtsA), microbial metabolism in diverse environments (FadB, GpmA, PfkB, NfnB, TalA, FbaB), and ABC transporters (PstS, YbeJ, MglB, RbsB, ArtJ). Proteins found down-regulated are involved mainly in carbon metabolism (FadB, GpmA, PfkB, FalA, FbaB) and the biosynthesis of amino acids (GpmA, PfkB, TalA, FbaB). Most of the identified differential proteins were predicted to be antigenic, and matched with resistome data. Conclusions: A total of 28 proteins were up-regulated, and 9 were down-regulated in XDR S. Typhi. Further characterization of the identified proteins will help in understanding the molecular signaling involved in the emergence of XDR S. Typhi. Full article

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. Full article

Salmonella enterica serovar Typhi (S. Typhi) is a Gram-negative pathogen that causes typhoid fever in humans. Though many serotypes of Salmonella spp. are capable of causing disease in both humans and animals alike, S. Typhi and S. Paratyphi are common in human hosts only. The global burden of typhoid fever is attributable to more than 27 million cases each year and approximately 200,000 deaths worldwide, with many regions such as Africa, South and Southeast Asia being the most affected in the world. The pathogen is able to cause disease in hosts by evading defense systems, adhesion to epithelial cells, and survival in host cells in the presence of several virulence factors, mediated by virulence plasmids and genes clustered in distinct regions known as Salmonella pathogenicity islands (SPIs). These factors, coupled with plasmid-mediated antimicrobial resistance genes, enable the bacterium to become resistant to various broad-spectrum antibiotics used in the treatment of typhoid fever and other infections caused by Salmonella spp. The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains in many countries of the world has raised great concern over the rise of antibiotic resistance in pathogens such as S. Typhi. In order to identify the key virulence factors involved in S. Typhi pathogenesis and infection, this review delves into various mechanisms of virulence, pathogenicity, and antimicrobial resistance to reinforce efficacious disease management. Full article

Salmonella Typhi is a Gram-negative pathogen that causes typhoid fever in humans. The use of antibiotics to treat typhoid has considerably mitigated its fatality risk, but rising multidrug-resistant (MDR) and extensively drug-resistant (XDR) resistance in Pakistan threatens effective treatment. This study determined the prevalence of MDR and XDR S. Typhi at a local hospital in Lahore. Blood samples (n = 3000) were obtained and processed for bacterial identification. Antibiotic susceptibility test was performed using VITEK^® 2 Compound 30 System. Statistical data analysis was performed using a Mann–Whitney U and Kruskal–Wallis H test, respectively. The results revealed 600 positive cultures, of which the majority were found to be XDR S. Typhi (46.1%) and MDR S. Typhi (24.5%) strains. The disease burden of resistant Salmonella strains was greater in males (60.67%) than females (39.33%), with the most affected age group being 0–10 years old (70.4 %). In both the outpatient department (OPD) and general ward, the prevalence of XDR S. Typhi cases was found to be alarmingly high (48.24%), followed by MDR S. Typhi (25.04 %). The results of the statistical analysis demonstrated that the incidence of resistance in MDR and XDR S. Typhi strains was not affected by the age as well as the gender of patients (p > 0.05). The occurrence of resistant strains against four tested antibiotics (azithromycin, ciprofloxacin, imipenem, and meropenem) was found to be similar in different wards and among hospitalized and OPD patients (p > 0.05). Maximum resistance was observed against chloramphenicol and ampicillin in the OPD and pediatric ward. Piperacillin/Tazobactam was observed to be the most effective antibiotic, followed by co-amoxiclav (p < 0.001). This study is effective in validating the existence of MDR and XDR S. Typhi in Lahore, where stringent methods should be applied for controlling its spread. Full article

Salmonella enterica serovar Typhi (S. Typhi) and S. Paratyphi, namely typhoidal Salmonellae, are the cause of (para) typhoid fever, which is a devastating systemic infectious disease in humans. In addition, the spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) S. Typhi in many low and middle-income countries poses a significant risk to human health. While currently available typhoid vaccines and therapeutics are efficacious, they have some limitations. One important limitation is the lack of controlling individuals who chronically carry S. Typhi. However, due to the strict host specificity of S. Typhi to humans, S. Typhi research is hampered. As a result, our understanding of S. Typhi pathogenesis is incomplete, thereby delaying the development and improvement of prevention and treatment strategies. Nonetheless, to better combat and contain S. Typhi, it is vital to develop a vaccine and therapy for controlling both acutely and chronically infected individuals. This review discusses how scientists are trying to combat typhoid fever, why it is so challenging to do so, which approaches show promise, and what we know about the pathogenesis of S. Typhi chronic infection. Full article