Trends in antimicrobial resistance amongst Salmonella Typhi in Bangladesh: A 24-year retrospective observational study (1999-2022).

BACKGROUND: Rising antimicrobial resistance (AMR) in Salmonella Typhi restricts typhoid treatment options, heightening concerns for pan-oral drug-resistant outbreaks. However, lack of long-term temporal surveillance data on AMR in countries with high burden like Bangladesh is scarce. Our study explores the AMR trends of Salmonella Typhi isolates from Bangladesh, drawing comparisons with antibiotic consumption to optimize antibiotic stewardship strategies for the country. METHODOLOGY/PRINCIPAL FINDINGS: The typhoid fever surveillance from 1999 to 2022 included two pediatric hospitals and three private clinics in Dhaka, Bangladesh. Blood cultures were performed at treating physicians' discretion; cases were confirmed by microbiological, serological, and biochemical tests. Antibiotic susceptibility was determined following CLSI guidelines. National antibiotic consumption data for cotrimoxazole, ciprofloxacin, and azithromycin was obtained from IQVIA-MIDAS database for comparison. Over the 24 years of surveillance, we recorded 12,435 culture-confirmed typhoid cases and observed declining resistance to first-line drugs (amoxicillin, chloramphenicol, and cotrimoxazole); multidrug resistance (MDR) decreased from 38% in 1999 to 17% in 2022. Cotrimoxazole consumption dropped from 0.8 to 0.1 Daily defined doses (DDD)/1000/day (1999-2020). Ciprofloxacin non-susceptibility persisted at >90% with unchanged consumption (1.1-1.3 DDD/1000/day, 2002-2020). Low ceftriaxone resistance (<1%) was observed, with slightly rising MIC (0.03 to 0.12 mg/L, 1999-2019). Azithromycin consumption increased (0.1 to 3.8 DDD/1000/day, 1999-2020), but resistance remained ≤4%. CONCLUSION: Our study highlights declining MDR amongst Salmonella Typhi in Bangladesh; first-line antimicrobials could be reintroduced as empirical treatment options for typhoid fever if MDR rates further drops below 5%. The analysis also provides baseline data for monitoring the impact of future interventions like typhoid conjugate vaccines on typhoid burden and associated AMR.

Spermine induced endogenous signal ameliorates osmotic stress in Lens culinaris.

The present study evaluates the alleviation of polyethylene glycol (PEG) mediated osmotic stress by exogenous spermine (SP) application on seeds of Lens culinaris. Seeds were soaked overnight with SP (0.05 M) and PEG (10%) separately. Third set was prepared by combined treatment with SP (0.05 M) and PEG (10%). Further, various physiological parameters, defense enzymes, phenol, flavonoid, nitric oxide (NO), proline content, chromosomal abnormality studies etc. was conducted after 5 days of incubation. PEG application significantly hampered the seed germination, root length, shoot length, relative water content and vigour index. Application of PEG induced electrolytic leakage in root cells. PEG application also significantly reduced the activities of different defense parameters viz. peroxidase, polyphenol oxidase, phenylalanine ammonia lyase and ß-1,3 glucanase, total phenol and flavonoid accumulation over control. Reactive oxygen species, lipid peroxidation, cell death was found significantly high in PEG treated sets. However, NO level has been significantly decreased by PEG treatment. Cytological studies showed reduced mitotic index and highest abnormalities under osmotic stress. Contrary to that, application of SP either alone or in combination with PEG showed improved responses of aforesaid defense parameters compared to control and solely PEG treated sets. Interestingly, cytological abnormalities were also reduced in SP treated roots. Overall, these results suggests that SP application on seeds reduced the PEG induced damage and intricately improved the defense mechanisms which might help to fight against oxidative stress.

Trends in antimicrobial resistance amongst Salmonella Paratyphi A isolates in Bangladesh: 1999-2021.

BACKGROUND: Typhoid and paratyphoid remain common bloodstream infections in areas with suboptimal water and sanitation infrastructure. Paratyphoid, caused by Salmonella Paratyphi A, is less prevalent than typhoid and its antimicrobial resistance (AMR) trends are less documented. Empirical treatment for paratyphoid is commonly based on the knowledge of susceptibility of Salmonella Typhi, which causes typhoid. Hence, with rising drug resistance in Salmonella Typhi, last-line antibiotics like ceftriaxone and azithromycin are prescribed for both typhoid and paratyphoid. However, unlike for typhoid, there is no vaccine to prevent paratyphoid. Here, we report 23-year AMR trends of Salmonella Paratyphi A in Bangladesh. METHODS: From 1999 to 2021, we conducted enteric fever surveillance in two major pediatric hospitals and three clinics in Dhaka, Bangladesh. Blood cultures were performed at the discretion of the treating physicians; cases were confirmed by culture, serological and biochemical tests. Antimicrobial susceptibility was determined following CLSI guidelines. RESULTS: Over 23 years, we identified 2,725 blood culture-confirmed paratyphoid cases. Over 97% of the isolates were susceptible to ampicillin, chloramphenicol, and cotrimoxazole, and no isolate was resistant to all three. No resistance to ceftriaxone was recorded, and >99% of the isolates were sensitive to azithromycin. A slight increase in minimum inhibitory concentration (MIC) is noticed for ceftriaxone but the current average MIC is 32-fold lower than the resistance cut-off. Over 99% of the isolates exhibited decreased susceptibility to ciprofloxacin. CONCLUSIONS: Salmonella Paratyphi A has remained susceptible to most antibiotics, unlike Salmonella Typhi, despite widespread usage of many antibiotics in Bangladesh. The data can guide evidence-based policy decisions for empirical treatment of paratyphoid fever, especially in the post typhoid vaccine era, and with the availability of new paratyphoid diagnostics.

Ethnopharmacological Potential of Phytochemicals and Phytogenic Products against Human RNA Viral Diseases as Preventive Therapeutics.

RNA viruses have been the most destructive due to their transmissibility and lack of control measures. Developments of vaccines for RNA viruses are very tough or almost impossible as viruses are highly mutable. For the last few decades, most of the epidemic and pandemic viral diseases have wreaked huge devastation with innumerable fatalities. To combat this threat to mankind, plant-derived novel antiviral products may contribute as reliable alternatives. They are assumed to be nontoxic, less hazardous, and safe compounds that have been in uses in the beginning of human civilization. In this growing COVID-19 pandemic, the present review amalgamates and depicts the role of various plant products in curing viral diseases in humans.

Estimating typhoid incidence from community-based serosurveys: a multicohort study.

BACKGROUND: The incidence of enteric fever, an invasive bacterial infection caused by typhoidal Salmonellae (Salmonella enterica serovars Typhi and Paratyphi), is largely unknown in regions without blood culture surveillance. The aim of this study was to evaluate whether new diagnostic serological markers for typhoidal Salmonella can reliably estimate population-level incidence. METHODS: We collected longitudinal blood samples from patients with blood culture-confirmed enteric fever enrolled from surveillance studies in Bangladesh, Nepal, Pakistan, and Ghana between 2016 and 2021 and conducted cross-sectional serosurveys in the catchment areas of each surveillance site. We used ELISAs to measure quantitative IgA and IgG antibody responses to hemolysin E and S Typhi lipopolysaccharide. We used Bayesian hierarchical models to fit two-phase power-function decay models to the longitudinal antibody responses among enteric fever cases and used the joint distributions of the peak antibody titres and decay rate to estimate population-level incidence rates from cross-sectional serosurveys. FINDINGS: The longitudinal antibody kinetics for all antigen-isotypes were similar across countries and did not vary by clinical severity. The seroincidence of typhoidal Salmonella infection among children younger than 5 years ranged between 58·5 per 100 person-years (95% CI 42·1-81·4) in Dhaka, Bangladesh, to 6·6 per 100 person-years (4·3-9·9) in Kavrepalanchok, Nepal, and followed the same rank order as clinical incidence estimates. INTERPRETATION: The approach described here has the potential to expand the geographical scope of typhoidal Salmonella surveillance and generate incidence estimates that are comparable across geographical regions and time. FUNDING: Bill & Melinda Gates Foundation. TRANSLATIONS: For the Nepali, Bengali and Urdu translations of the abstract see Supplementary Materials section.

Surgical Stent Guided Versus Conventional Method of Implant Placement.

Aim: The aim of this study is to compare the surgical accuracy and efficiency of endo-osseous implant placement using a conventional method and when placed using a custom surgical guide. Materials and methods: The study was carried out in a case control design on 20 patients aged between 15 years and 60 years. In the study group (n = 10) the implants were placed with the help of a surgical stent, while in the control group (n = 10) implants were placed in a conventional manner (without surgical stent) planned only with CBCT scan. The same surgeon placed the implants in both the groups. Results: Each patient was considered in terms of the number of implants received. Each planned and actual implant was compared in terms of the 8 quantitative variables, which were used to observe and compare the accuracy of the surgical guides and conventionally placed implants. Data were analysed by a single blinded statistician using statistical software (Graphpad Prism (Version 5)). The Microsoft excel and Student T test for parametric data and Chi-square test for categorical data were used to observe significant differences between the 2 study groups. The nonparametric Chi-Square test revealed a statistically significant difference between surgical stent guided and conventional surgery in terms of buccal and lingual/palatal cortical plate to implant deviation, adjacent tooth to implant deviation, and mesiodistal angular deviation, whereas the differences between the marginal bone loss deviation, stability deviation, pain and swelling deviation, treatment time and number of sessions deviation, satisfaction deviation were not statistically significant. Conclusion: From our study, we can conclude that guided surgery is essential for insertion of the implants regardless of the surgical technique. The success of the guided surgery depends on accuracy of the clinical and/or laboratorial steps of the virtual planning. Despite all the limitations and probability of errors encountered in our study, the guided surgery is superior in better positioning of implants.

Chitosan nanoparticles mitigate Alternaria leaf spot disease of chilli in nitric oxide dependent way.

The present study focuses on protection of emerging Alternaria leaf spot disease of chilli by application of chitosan nanoparticles (CNP). CNP was prepared by ionotropic gelation method and characterized. Antifungal potential of CNP was also checked against Alternaria alternata and its mechanisms were unraveled. Foliar application of CNP (0.001%) improved plant innate immunity in two chilli cultivars (one tolerant and one susceptible) by inducing the activities of different defense related enzymes along with total phenol and flavonoid. CNP application also induced callose deposition and reduced cell death in both the cultivar. Signaling molecule nitric oxide (NO) also augmented in CNP treated sets which were confirmed by both biochemical and microscopic data. In order to find out involvement of NO in CNP induced innate immunity in chilli cultivars, both NO surplus and NO depleted conditions were artificially created and defense responses were recorded. It was interesting to note that CNP mediated enhancement of defense responses in chilli plants was compromised in NO depleted condition. These results signify possible involvement of NO in CNP induced defense responses in chilli plants. It is evident from our results that CNP can be used to protect chilli plants against this fungal disease to develop a sustainable management strategy.

Suprapubic penetrating abdominal trauma - defining peritoneal breach and choices in operative intervention.

Penetrating abdominal trauma is an uncommon cause of presentation to emergency departments in Australia and is frequently associated with the clinical need for emergent operative intervention. Advances in imaging modalities, improved laparoscopic techniques and structured approaches to resuscitation in trauma have now allowed potential minimally invasive management of such injuries, avoiding laparotomy and therefore defining peritoneal breach; the major determinant of intra-abdominal organ injury in this setting is critical. We present the case of a self-inflicted stab injury to the suprapubic region in an otherwise healthy man and describe the combination of imaging and operative modalities used to define peritoneal breach in this case which successfully reduced the patient's morbidity by avoiding non-therapeutic laparotomy.

Interaction between Bean and Colletotrichum gloeosporioides: Understanding Through a Biochemical Approach.

In addition to its role in animals, nowadays nitric oxide (NO) is considered as an emerging signaling molecule in plant systems. It is now believed that NO exerts its pivotal role in various plant physiological processes, such as in seed germination, plant developmental stages, and plant defense mechanisms. In this study, we have taken an initiative to show the biochemical basis of defense response activation in bean leaves during the progression of Colletotrichum gloeosporioides (Penz.) Penz. and Sacc. in detached bean leaves. Stages of pathogen penetration and colonization were successfully established in the detached bean leaves. Results showed up-regulation of different defense-related enzymes and other defense molecules, such as phenols, flavonoids, callose, and lignin molecules, along with NO at early stages of pathogen invasion. Although in the later stages of the disease, development of NO and other defense components (excluding lignin) were down-regulated, the production of reactive oxygen species in the form of H2O2 became elevated. Consequently, other stress markers, such as lipid peroxidation, proline content, and chlorophyll content, were changed accordingly. Correlation between the disease index and other defense molecules, along with NO, indicate that production of NO and reactive oxygen species (ROS) might influence the development of anthracnose in common bean.

Progression and survival results after radical hepatic metastasectomy of indolent advanced neuroendocrine neoplasms (NENs) supports an aggressive surgical approach.

BACKGROUND: Neuroendocrine neoplasms most commonly metastasize to the liver. Operative extirpation of neuroendocrine neoplasm hepatic metastases improves symptoms and seems to improve survival, but subsequent evidence is required. The current study evaluates the progression-free survival and overall survival of patients after resection (with or without ablation) of neuroendocrine neoplasm hepatic metastases. As a secondary endpoint, the prognostic factors associated with progression-free survival and overall survival were evaluated. METHODS: Seventy-four patients with neuroendocrine neoplasm hepatic metastases underwent hepatic resection between December 1992 and December 2009. Thirty-eight patients underwent synchronous cryoablation. Patients were assessed radiologically and serologically at monthly intervals for the first 3 months and then at 6-month intervals after treatment. Progression-free survival and overall survival were determined; clinicopathologic and treatment-related factors associated with progression-free survival and overall survival were evaluated through univariate and multivariate analyses. RESULTS: No patient was lost to follow-up. The median follow-up for the patients who were alive was 41 months (range, 1-162). The median progression-free survival and overall survival after hepatic resection were 23 and 95 months, respectively. Five- and 10-year overall survival were 63% and 40%, respectively. Two independent factors were associated with overall survival: histologic grade (P < .001) and extrahepatic disease (P = .021). The only independent predictor for progression-free survival was pathologic margin status (P = .023). CONCLUSION: In selected patients, aggressive operative extirpation of neuroendocrine neoplasm hepatic metastases is effective in achieving long-term survival. Disease progression, however, is a common occurrence; therefore, a multimodality treatment approach for progressive disease is necessary. Integrating the knowledge of identified prognostic factors can both improve patient selection and identify patients at greatest risk of treatment failure.

Clinicopathologic and treatment-related factors influencing recurrence and survival after hepatic resection of intrahepatic cholangiocarcinoma: a 19-year experience from an established Australian hepatobiliary unit.

BACKGROUND: Intrahepatic cholangiocarcinoma is rare, but its incidence is rapidly increasing in developed countries. Early detection and surgical extirpation offer the only hope for cure. Given the rarity of intrahepatic cholangiocarcinoma, there is limited knowledge regarding its natural history, clinicopathological characteristics, or outcomes following surgery. The primary aim of the current study is to report overall survival and recurrence-free survival outcomes following resection of intrahepatic cholangiocarcinoma. The secondary aim is to evaluate the impact of prognostic variables on outcomes. METHODS: Between November 1990 and November 2009, 88 patients were evaluated for their suitability for potentially curative surgery; of these, 40 patients underwent potentially curative surgery. These patients are the principal subjects of the current analysis. Patients were assessed at monthly intervals for the first 3 months and then at six monthly intervals after treatment. Recurrence-free survival and overall survival were determined; 17 clinicopathological and treatment-related factors associated with recurrence-free survival and overall survival were evaluated through univariate and multivariate analyses. RESULTS: No patient was lost to follow-up. The median follow-up was 31 months (range = 0-142 months). The median recurrence-free survival and overall survival after resection were 21 and 33 months, respectively. The 5-year survival rate was 28%. Four factors were associated with overall survival: carbohydrate antigen 19.9 (p = 0.020), clinical stage (p = 0.018), histological grade (p = 0.020), and lymph node metastases (p = 0.003). Two factors were associated with recurrence-free survival: carbohydrate antigen 19.9 (p = 0.002) and margin status (p = 0.002). CONCLUSION: Hepatic resection is an efficacious treatment for intrahepatic cholangiocarcinoma. Clincopathological factors can predict outcome and should be used in the preoperative assessment of operability.