The Prospective Effect of Cinnamon and Chia on Submandibular Salivary Glands After Ciprofloxacin Administration in Albino Rats (Histological, Histochemical, and Ultrastructural Study).

Ciprofloxacin (CPFX®) is potent fluoroquinolone but has severe side effects. Cinnamon (CIN) and chia seeds are potent antioxidants. The current work aimed to compare the effect of CIN extract and chia seeds on CPFX®-treated submandibular salivary glands (SMGs). Thirty-two male albino rats were divided into four groups: Group 1: received saline. Group 2: received CPFX®. Group 3: received CIN extract after 4 h of CPFX® administration. Group 4: received ground chia seeds after 4 h of CPFX® administration. After 10 days, histological, histochemical, and ultrastructural examinations were done. Different examinations illustrated normal features of SMG in Groups 1 and 3. Group 2 showed degenerative signs. Group 4 showed normal features in some areas. Statistical results illustrated that Group 2 had highest mean vacuolation area%. Highest mean of PAS optical density (OD) was for Group 2. Concerning mercuric bromophenol blue stain OD; Group 1 showed highest mean OD. CPFX® has the deteriorative effect on SMG structure and ultrastructure. It leads to increased levels of glycosaminoglycans (GAGs) and decreased levels of total proteins. CIN extract showed more ameliorative effect compared to chia seeds.

Transcriptome Profile Identifies Actin as an Essential Regulator of Cardiac Myosin Binding Protein C3 Hypertrophic Cardiomyopathy in a Zebrafish Model.

Variants in cardiac myosin-binding protein C (cMyBP-C) are the leading cause of inherited hypertrophic cardiomyopathy (HCM), demonstrating the key role that cMyBP-C plays in the heart's contractile machinery. To investigate the c-MYBPC3 HCM-related cardiac impairment, we generated a zebrafish mypbc3-knockout model. These knockout zebrafish displayed significant morphological heart alterations related to a significant decrease in ventricular and atrial diameters at systolic and diastolic states at the larval stages. Immunofluorescence staining revealed significant hyperplasia in the mutant's total cardiac and ventricular cardiomyocytes. Although cardiac contractility was similar to the wild-type control, the ejection fraction was significantly increased in the mypbc3 mutants. At later stages of larval development, the mutants demonstrated an early cardiac phenotype of myocardium remodeling, concurrent cardiomyocyte hyperplasia, and increased ejection fraction as critical processes in HCM initiation to counteract the increased ventricular myocardial wall stress. The examination of zebrafish adults showed a thickened ventricular cardiac wall with reduced heart rate, swimming speed, and endurance ability in both the mypbc3 heterozygous and homozygous groups. Furthermore, heart transcriptome profiling showed a significant downregulation of the actin-filament-based process, indicating an impaired actin cytoskeleton organization as the main dysregulating factor associated with the early ventricular cardiac hypertrophy in the zebrafish mypbc3 HCM model.

ESBL-producing strains isolated from imported cases of enteric fever in England and Wales reveal multiple chromosomal integrations of blaCTX-M-15 in XDR Salmonella Typhi.

BACKGROUND: There are approximately 300 cases of enteric fever reported annually from England and Wales; most are imported infections. Clinical management of enteric fever remains a challenge with the emergence of ESBL-producing strains, especially XDR Salmonella Typhi from Sindh, Pakistan. METHODS: All strains of S. Typhi and Salmonella Paratyphi A isolated from cases presenting with symptoms of enteric fever in England and Wales, between 1 April 2014 and 31 March 2020, were characterized using WGS. Antibiotic susceptibility testing was performed using an agar dilution method. RESULTS: ESBL strains contributed to 69 cases of enteric fever (S. Typhi n = 68, S. Paratyphi A n = 1); 68 were imported (Pakistan n = 64, Iraq n = 2, Bangladesh n = 1 and India n = 1). Ages ranged from 1 to 56 years, 36/69 (52%) were children, 52% were female and the duration of hospital stay ranged from 1 to 23 days. The ESBL phenotype was conferred by the presence of blaCTX-M-15 (S. Typhi n = 67 and S. Paratyphi A n = 1) or blaCTX-M-55 (S. Typhi n = 1). An IncY plasmid harbouring blaCTX-M-15 and qnr was detected in 56 strains from Pakistan. The IncY plasmid was absent in the remaining strains and there was evidence of a 4 kb ISEcpl-blaCTX-M-15-tnp gene cassette insertion into the chromosome at one of three integration points. CONCLUSIONS: Chromosomal integration of blaCTX-M-15 within the XDR Sindh strains may lead to the maintenance of resistance in the absence of antibiotic selection pressure. Empirical treatment of cases of complicated enteric fever returning from Pakistan will henceforth have to include a carbapenem.

Functional characterization of human myosin-binding protein C3 variants associated with hypertrophic cardiomyopathy reveals exon-specific cardiac phenotypes in zebrafish model.

Myosin-binding protein C 3 (MYBPC3) variants are the most common cause of hypertrophic cardiomyopathy (HCM). HCM is a complex cardiac disorder due to its significant genetic and clinical heterogeneity. MYBPC3 variants genotype-phenotype associations remain poorly understood. We investigated the impact of two novel human MYBPC3 splice-site variants: V1: c.654+2_654+4dupTGG targeting exon 5 using morpholino MOe5i5; and V2: c.772+1G>A targeting exon 6 using MOe6i6; located within C1 domain of cMyBP-C protein, known to be critical in regulating sarcomere structure and contractility. Zebrafish MOe5i5 and MOe6i6 morphants recapitulated typical characteristics of human HCM with cardiac phenotypes of varying severity, including reduced cardiomyocyte count, thickened ventricular myocardial wall, a drastic reduction in heart rate, stroke volume, and cardiac output. Analysis of all cardiac morphological and functional parameters demonstrated that V2 cardiac phenotype was more severe than V1. Coinjection with synthetic human MYBPC3 messenger RNA (mRNA) partially rescued disparate cardiac phenotypes in each zebrafish morphant. While human MYBPC3 mRNA partially restored the decreased heart rate in V1 morphants and displayed increased percentages of ejection fraction, fractional shortening, and area change, it failed to revert the V1 ventricular myocardial thickness. These results suggest a possible V1 impact on cardiac contractility. In contrast, attempts to rescue V2 morphants only restored the ventricular myocardial wall hypertrophy phenotype but had no significant effect on impaired heart rate, suggesting a potential V2 impact on the cardiac structure. Our study provides evidence of an association between MYBPC3 exon-specific cardiac phenotypes in the zebrafish model providing important insights into how these genetic variants contribute to HCM disease.

Comparative study between the efficacy of fractional micro-needle radiofrequency and fractional CO2 laser in the treatment of striae distensae.

Striae distensae (SD) cause a cosmetic problem to many patients. Recently, fractional micro-needle radiofrequency (FMR) device has been introduced in treatment of SD. Also, fractional CO2 laser has been used as a resurfacing laser technique in the treatment of SD. The aim of our study was to assess and compare between the efficacy of FMR and fractional CO2 laser in treatment of SD. Seventeen female patients with SD were enrolled in this study. Detailed history was taken and dermatological examination was done to determine the type of striae, the location, and measurement of the width of the largest striae on each side. In each patient, one side was randomly assigned to treatment by FMR (area A), and the other side to treatment by fractional CO2 laser (area B). Our results showed that both techniques were effective. A slight better efficacy was encountered with FMR, but the difference was not statistically significant (p = 0.716). The current study concluded that FMR and fractional CO2 laser are almost equally effective in the treatment of SD (rubra and alba). Development of post inflammatory hyper-pigmentation (PIH) was evident with fractional CO2 in contrast with FMR, and the difference was statistically significant (p = 0.001).

The Role of Cardiac Myosin Binding Protein C3 in Hypertrophic Cardiomyopathy-Progress and Novel Therapeutic Opportunities.

Hypertrophic cardiomyopathy (HCM) is a common autosomal dominant genetic cardiovascular disorder marked by genetic and phenotypic heterogeneity. Mutations in the gene encodes the cardiac myosin-binding protein C, cMYBPC3 is amongst the various sarcomeric genes that are associated with HCM. These mutations produce mutated mRNAs and truncated cMyBP-C proteins. In this review, we will discuss the implications and molecular mechanisms involved in MYBPC3 different mutations. Further, we will highlight the novel targets that can be developed into potential therapeutics for the treatment of HMC. J. Cell. Physiol. 232: 1650-1659, 2017. © 2016 Wiley Periodicals, Inc.

Targeting osteopontin, the silent partner of Na+/H+ exchanger isoform 1 in cardiac remodeling.

Cardiac hypertrophy (CH), characterized by the enlargement of cardiomyocytes, fibrosis and apoptosis, contributes to cardiac remodeling, which if left unresolved results in heart failure. Understanding the signaling pathways underlying CH is necessary to identify potential therapeutic targets. The Na(+) /H(+) -exchanger isoform I (NHE1), a ubiquitously expressed glycoprotein and cardiac specific isoform, regulates intracellular pH. Recent studies have demonstrated that enhanced expression/activity of NHE1 contributes to cardiac remodeling and CH. Inhibition of NHE1 in both in vitro and in vivo models have suggested that inhibition of NHE1 protects against hypertrophy. However, clinical trials using NHE1 inhibitors have proven to be unsuccessful, suggesting that additional factors maybe contributing to cardiac remodeling. Recent studies have indicated that the upregulation of NHE1 is associated with enhanced levels of osteopontin (OPN) in the setting of CH. OPN has been demonstrated to be upregulated in left ventricular hypertrophy, dilated cardiomyopathy and in diabetic cardiomyopathy. The cellular interplay between OPN and NHE1 in the setting of CH remains unknown. This review focuses on the role of NHE1 and OPN in cardiac remodeling and emphasizes the signaling pathways implicating OPN in the NHE1-induced hypertrophic response.

Na(+)/H (+) exchanger isoform 1 induced osteopontin expression in cardiomyocytes involves NFAT3/Gata4.

Osteopontin (OPN), a multifunctional glycophosphoprotein, has been reported to contribute to the development and progression of cardiac remodeling and hypertrophy. Cardiac-specific OPN knockout mice were protected against hypertrophy and fibrosis mediated by Ang II. Recently, transgenic mice expressing the active form of the Na(+)/H(+) exchanger isoform 1 (NHE1) developed spontaneous hypertrophy in association with elevated levels of OPN. The mechanism by which active NHE1 induces OPN expression and contributes to the hypertrophic response remains unclear. To validate whether expression of the active form of NHE1 induces OPN, cardiomyocytes were stimulated with Ang II, a known inducer of both OPN and NHE1. Ang II induced hypertrophy and increased OPN protein expression (151.6 ± 28.19 %, P < 0.01) and NHE1 activity in H9c2 cardiomyoblasts. Ang II-induced hypertrophy and OPN protein expression were regressed in the presence of an NHE1 inhibitor, EMD 87580, or a calcineurin inhibitor, FK506. In addition, our results indicated that activation of NHE1-induced NFAT3 translocation into the nucleus and a significant activation of the transcription factor Gata4 (NHE1: 149 ± 28 % of control, P < 0.05). NHE1-induced activation of Gata4 was inhibited by FK506. In summary, our results suggest that activation of NHE1 induces hypertrophy through the activation of NFAT3/Gata4 and OPN expression.

A review of obesity, insulin resistance, and the role of exercise in breast cancer patients.

Breast cancer, the most common female malignancy in the world, has a strong association with obesity and insulin resistance. The importance of these risk factors goes up significantly in patients already affected by this cancer as they negatively affect the prognosis, recurrence rate, and survival by various mechanisms. The literature on the role of physical activity and aerobic exercise on modifying the above risks is debatable with data both for and against it. In this article, we have reviewed the risks of obesity and insulin resistance in breast cancer patients and the controversy associated with the impact of exercise. Ultimately, we have concluded that a randomized control trial is necessary with an individualized aerobic exercise program for a minimum duration of 20 wk on breast cancer patients, who are undergoing or recently completed chemotherapy, to study its effects on insulin resistance, weight, and clinical outcome.

A case of life-threatening retinoic acid syndrome and review of literature.

All-trans-retinoic acid represents a major progress that has made acute promyelocytic leukemia the most curable subtype of acute myeloid leukemia in adults. Although all-trans-retinoic acid is usually well tolerated, some patients develop the retinoic acid syndrome, characterized by unexplained fever, weight gain, respiratory distress, interstitial pulmonary infiltrates, pleural and pericardial effusions, episodic hypotension, and acute renal failure. Further studies of growth factor expression and modulation of adhesion molecules are warranted to provide further insights into the pathogenesis of the syndrome and may lead to its prevention.

Fear in general populations: A cross-sectional study on perceived fear of common diseases, COVID-19, life events, and environmental threats in 30 countries.

Background: In this study, we assessed the general population's fears towards various diseases and events, aiming to inform public health strategies that balance health-seeking behaviours. Methods: We surveyed adults from 30 countries across all World Health Organization (WHO) regions between July 2020 and August 2021. Participants rated their fear of 11 factors on an 11-point Likert scale. We stratified the data by age and gender and examined variations across countries and regions through multidimensional preference analysis. Results: Of the 16 512 adult participants, 62.7% (n = 10 351) were women. The most feared factor was the loss of family members, reported by 4232 participants (25.9%), followed by cancer (n = 2248, 13.7%) and stroke (n = 1416, 8.7%). The highest weighted fear scores were for loss of family members (mean (x̄) = 7.46, standard deviation (SD) = 3.04), cancer (x̄ = 7.00, SD = 3.09), and stroke (x̄ = 6.61, SD = 3.24). The least feared factors included animals/insects (x̄ = 3.72, SD = 2.96), loss of a mobile phone (x̄ = 4.27, SD = 2.98), and social isolation (x̄ = 4.83, SD = 3.13). Coronavirus disease 2019 (COVID-19) was the sixth most feared factor (x̄ = 6.23, SD = 2.92). Multidimensional preference analyses showed distinct fears of COVID-19 and job loss in Australia and Burundi. The other countries primarily feared loss of family members, cancer, stroke, and heart attacks; this ranking was consistent across WHO regions, economic levels, and COVID-19 severity levels. Conclusions: Fear of family loss can improve public health messaging, highlighting the need for bereavement support and the prevention of early death-causing diseases. Addressing cancer fears is crucial to encouraging the use of preventive services. Fear of non-communicable diseases remains high during health emergencies. Top fears require more resources and countries with similar concerns should collaborate internationally for effective fear management.

Key lifestyles and health outcomes across 16 prevalent chronic diseases: A network analysis of an international observational study.

Background: Central and bridge nodes can drive significant overall improvements within their respective networks. We aimed to identify them in 16 prevalent chronic diseases during the coronavirus disease 2019 (COVID-19) pandemic to guide effective intervention strategies and appropriate resource allocation for most significant holistic lifestyle and health improvements. Methods: We surveyed 16 512 adults from July 2020 to August 2021 in 30 territories. Participants self-reported their medical histories and the perceived impact of COVID-19 on 18 lifestyle factors and 13 health outcomes. For each disease subgroup, we generated lifestyle, health outcome, and bridge networks. Variables with the highest centrality indices in each were identified central or bridge. We validated these networks using nonparametric and case-dropping subset bootstrapping and confirmed central and bridge variables' significantly higher indices through a centrality difference test. Findings: Among the 48 networks, 44 were validated (all correlation-stability coefficients >0.25). Six central lifestyle factors were identified: less consumption of snacks (for the chronic disease: anxiety), less sugary drinks (cancer, gastric ulcer, hypertension, insomnia, and pre-diabetes), less smoking tobacco (chronic obstructive pulmonary disease), frequency of exercise (depression and fatty liver disease), duration of exercise (irritable bowel syndrome), and overall amount of exercise (autoimmune disease, diabetes, eczema, heart attack, and high cholesterol). Two central health outcomes emerged: less emotional distress (chronic obstructive pulmonary disease, eczema, fatty liver disease, gastric ulcer, heart attack, high cholesterol, hypertension, insomnia, and pre-diabetes) and quality of life (anxiety, autoimmune disease, cancer, depression, diabetes, and irritable bowel syndrome). Four bridge lifestyles were identified: consumption of fruits and vegetables (diabetes, high cholesterol, hypertension, and insomnia), less duration of sitting (eczema, fatty liver disease, and heart attack), frequency of exercise (autoimmune disease, depression, and heart attack), and overall amount of exercise (anxiety, gastric ulcer, and insomnia). The centrality difference test showed the central and bridge variables had significantly higher centrality indices than others in their networks (P < 0.05). Conclusion: To effectively manage chronic diseases during the COVID-19 pandemic, enhanced interventions and optimised resource allocation toward central lifestyle factors, health outcomes, and bridge lifestyles are paramount. The key variables shared across chronic diseases emphasise the importance of coordinated intervention strategies.

Local therapy in metastatic breast cancer is associated with improved survival.

Patients presenting with stage-IV breast cancer are usually offered systemic chemotherapy to control metastatic tumor burden and palliative radiation therapy to manage the symptomatic primary tumor. The aim of this study was to assess the result of local therapy on the overall outcome of patients with metastatic breast cancer. We reviewed medical records of all patients with metastatic breast cancer that presented to our institution between 2000 and 2009. Based on the treatment received, the patients were grouped as follows: group 1 included patients who underwent surgery and also received radiotherapy and chemotherapy/hormonal therapy, group 2 included patients who received radiotherapy and chemotherapy/hormonal therapy only, and group 3 included patients who received chemotherapy/hormonal therapy alone. Of the 37 patients included in the study, 10 patients were placed in group 1, 17 patients in group 2, and 10 patients in group 3. About 38% had high to anaplastic tumor grade, and 48% had ≥2 metastatic sites in the body. Overall, the average survival time was 3.13 years (range: 0-17 years). A significant difference in survival estimates was noted between groups 1, 2, and 3 with mean survival times of 8.83, 4.9, and 2.26 years, respectively (log rank χ = 10.44, P = 0.005). In age-adjusted multivariate Cox regression model (χ = 21.729, P= 0.001), high/anaplastic tumor grade (P = 0.036), African American race (P = 0.009), central nervous system metastasis (P = 0.003), group 2 (P = 0.006), and group 3 (P = 0.002) were associated with poor survival. Survival was not associated with estrogen and progesterone receptor and visceral or bone metastases. We conclude that aggressive local control of primary tumor in patients presenting with stage-IV breast cancer is associated with improved survival.

Global impacts of COVID-19 on lifestyles and health and preparation preferences: An international survey of 30 countries.

Background: The health area being greatest impacted by coronavirus disease 2019 (COVID-19) and residents' perspective to better prepare for future pandemic remain unknown. We aimed to assess and make cross-country and cross-region comparisons of the global impacts of COVID-19 and preparation preferences of pandemic. Methods: We recruited adults in 30 countries covering all World Health Organization (WHO) regions from July 2020 to August 2021. 5 Likert-point scales were used to measure their perceived change in 32 aspects due to COVID-19 (-2 = substantially reduced to 2 = substantially increased) and perceived importance of 13 preparations (1 = not important to 5 = extremely important). Samples were stratified by age and gender in the corresponding countries. Multidimensional preference analysis displays disparities between 30 countries, WHO regions, economic development levels, and COVID-19 severity levels. Results: 16 512 adults participated, with 10 351 females. Among 32 aspects of impact, the most affected were having a meal at home (mean (m) = 0.84, standard error (SE) = 0.01), cooking at home (m = 0.78, SE = 0.01), social activities (m = -0.68, SE = 0.01), duration of screen time (m = 0.67, SE = 0.01), and duration of sitting (m = 0.59, SE = 0.01). Alcohol (m = -0.36, SE = 0.01) and tobacco (m = -0.38, SE = 0.01) consumption declined moderately. Among 13 preparations, respondents rated medicine delivery (m = 3.50, SE = 0.01), getting prescribed medicine in a hospital visit / follow-up in a community pharmacy (m = 3.37, SE = 0.01), and online shopping (m = 3.33, SE = 0.02) as the most important. The multidimensional preference analysis showed the European Region, Region of the Americas, Western Pacific Region and countries with a high-income level or medium to high COVID-19 severity were more adversely impacted on sitting and screen time duration and social activities, whereas other regions and countries experienced more cooking and eating at home. Countries with a high-income level or medium to high COVID-19 severity reported higher perceived mental burden and emotional distress. Except for low- and lower-middle-income countries, medicine delivery was always prioritised. Conclusions: Global increasing sitting and screen time and limiting social activities deserve as much attention as mental health. Besides, the pandemic has ushered in a notable enhancement in lifestyle of home cooking and eating, while simultaneously reducing the consumption of tobacco and alcohol. A health care system and technological infrastructure that facilitate medicine delivery, medicine prescription, and online shopping are priorities for coping with future pandemics.

Key lifestyles and interim health outcomes for effective interventions in general populations: A network analysis of a large international observational study.

Background: The interconnected nature of lifestyles and interim health outcomes implies the presence of the central lifestyle, central interim health outcome and bridge lifestyle, which are yet to be determined. Modifying these factors holds immense potential for substantial positive changes across all aspects of health and lifestyles. We aimed to identify these factors from a pool of 18 lifestyle factors and 13 interim health outcomes while investigating potential gender and occupation differences. Methods: An international cross-sectional study was conducted in 30 countries across six World Health Organization regions from July 2020 to August 2021, with 16 512 adults self-reporting changes in 18 lifestyle factors and 13 interim health outcomes since the pandemic. Results: Three networks were computed and tested. The central variables decided by the expected influence centrality were consumption of fruits and vegetables (centrality = 0.98) jointly with less sugary drinks (centrality = 0.93) in the lifestyles network; and quality of life (centrality = 1.00) co-dominant (centrality = 1.00) with less emotional distress in the interim health outcomes network. The overall amount of exercise had the highest bridge expected influence centrality in the bridge network (centrality = 0.51). No significant differences were found in the network global strength or the centrality of the aforementioned key variables within each network between males and females or health workers and non-health workers (all P-values >0.05 after Holm-Bonferroni correction). Conclusions: Consumption of fruits and vegetables, sugary drinks, quality of life, emotional distress, and the overall amount of exercise are key intervention components for improving overall lifestyle, overall health and overall health via lifestyle in the general population, respectively. Although modifications are needed for all aspects of lifestyle and interim health outcomes, a larger allocation of resources and more intensive interventions were recommended for these key variables to produce the most cost-effective improvements in lifestyles and health, regardless of gender or occupation.

Metastatic renal extraskeletal Ewing sarcoma in complete remission for the last 8 years.

Primary renal extraskeletal Ewing sarcoma (EES) is rare but well known to be aggressive, less responsive to the treatment, and has early predilection for metastases. Metastases at the time of diagnosis to the lungs or bones are associated with poor outcome. We present a case of primary renal EES in 57-year-old woman with multiple metastases to the lungs at the time of diagnosis with complete remission of the disease for the last 8 years following multimodality treatment Multidisciplinary approach for the management of EES has definitely improved the quality of life and the survival of the patients.

A case report of complete remission of pulmonary metastases from epithelioid sarcoma to navelbine chemotherapy.

Management of soft tissue sarcomas can be very challenging because they have a high rate of metastasis, especially to the lungs, and respond very poorly to the currently available chemotherapeutic drugs. We present a case of epithelioid sarcoma in which complete remission of pulmonary metastases was observed after treatment with a single agent, navelbine, a vinca alkaloid, and a potential therapeutic agent. The patient has been persistently free of metastases for 4 years since treatment with navelbine. Further studies are warranted to establish the role of navelbine for the treatment of soft tissue sarcoma and their metastases.

Gastrointestinal stromal tumor with primary resistance to imatinib and extensive bone metastases.

Gastrointestinal stromal tumors (GISTs) are the most common nonepithelial tumors of gastrointestinal tract characterized by mutations activating c-KIT or platelet-derived growth factor receptor alpha. GISTs frequently metastasize to liver and peritoneum, but rarely to the bones. Imatinib, a tyrosine kinase inhibitor, has revolutionized the treatment of advanced and metastasized GISTs by both slowing down the disease progression and prolonging the survival. Occasionally, patients with GISTs can develop primary or secondary resistance to imatinib monotherapy. We are presenting an interesting case of metastatic GISTs with extensive bone lesions and primary resistance to imatinib. Efforts to identify bone metastases using appropriate imaging modalities are highly recommended in patients diagnosed with GISTs. Also, alternate strategies to overcome the emerging resistance with single agent imatinib chemotherapy are warranted.

Carboplatin-induced hematuria in a patient of breast carcinoma. A case report.

Platinum-based antineoplastic drugs are widely used in the treatment of solid tumors. Carboplatin, a second generation platinum compound, was developed to have less nonhematologic toxicity, in comparison with cisplatin. We report on a 34-year-old woman with breast cancer who developed gross hematuria after initiation of carboplatin-based chemotherapy. To our knowledge, there are very few cases reports of carboplatin-associated gross hematuria.

Phylogenomics and antimicrobial resistance of Salmonella Typhi and Paratyphi A, B and C in England, 2016-2019.

The emergence of antimicrobial resistance (AMR) to first- and second-line treatment regimens of enteric fever is a global public-health problem, and routine genomic surveillance to inform clinical and public-health management guidance is essential. Here, we present the prospective analysis of genomic data to monitor trends in incidence, AMR and travel, and assess hierarchical clustering (HierCC) methodology of 1742 isolates of typhoidal salmonellae. Trend analysis of Salmonella Typhi and S. Paratyphi A cases per year increased 48 and 17.3%, respectively, between 2016 and 2019 in England, mainly associated with travel to South Asia. S. Paratyphi B cases have remained stable and are mainly associated with travel to the Middle East and South America. There has been an increase in the number of S. Typhi exhibiting a multidrug-resistant (MDR) profile and the emergence of extensively drug resistant (XDR) profiles. HierCC was a robust method to categorize clonal groups into clades and clusters associated with travel and AMR profiles. The majority of cases that had XDR S. Typhi reported recent travel to Pakistan (94 %) and belonged to a subpopulation of the 4.3.1 (H58) clone (HC5_1452). The phenotypic and genotypic AMR results showed high concordance for S. Typhi and S. Paratyphi A, B and C, with 99.99 % concordance and only three (0.01 %) discordant results out of a possible 23 178 isolate/antibiotic combinations. Genomic surveillance of enteric fever has shown the recent emergence and increase of MDR and XDR S. Typhi strains, resulting in a review of clinical guidelines to improve management of imported infections.