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Carbapenem resistance among bacteria, especially Klebsiella pneumoniae and Acinetobacter baumannii, constitutes a dreadful threat to public health all over the world that requires developing new medications urgently. Carbapenem resistance emerges as a serious problem as this class is used as a last-line option to clear the multidrug-resistant bacteria. Arthrospira maxima (Spirulina) is a well-known cyanobacterium used as a food supplement as it is rich in protein, essential minerals and vitamins and previous studies showed it may have some antimicrobial activity against different organisms. Biosynthesized (green) zinc oxide nanoparticles have been investigated by several researchers as antibacterials because of their safety in health. In this article, previous studies were analyzed to get to a conclusion about their activity as antibacterials. [ABSTRACT FROM AUTHOR]

Background: The emergence and spread of carbapenem resistance among Enterobacteriaceae, particularly Klebsiella pneumoniae, constitute a serious threat to public health, since carbapenems are the last line of defense in the treatment of life-threatening infections caused by drug-resistant Enterobacteriaceae. The current study investigated the co-existence of different virulence factors and carbapenemases in carbapenem-resistant Klebsiella pneumoniae clinical isolates from Alexandria, Egypt. Results: Phenotypic characterization of virulence factors indicated that 41.5% of the isolates were strong biofilm producers, while hypermucoviscosity was detected in 14.9% of the isolates. All isolates harbored five or more virulence factor encoding genes. entB, ycfM, mrkD and fimH were detected in all isolates, while only one isolate was negative for ybtS. uge, iutA, rmpA and kpn were detected in 61 (64.8%), 55 (58.5%), 41 (43.6%) and 27 (28.7%) isolates, respectively, while all isolates lacked magA and k2A. Phenotypic detection of carbapenemases was explored by performing CarbaNP and mCIM/eCIM. CarbaNP test showed positive results in 98.9% of the isolates and positive mCIM tests were observed in all isolates, while 68 (72.3%) isolates showed positive eCIM tests. blaNDM was the most prevalent carbapenemase encoding gene (92.5%) followed by the blaOXA−48 (51.1%), while blaKPC was detected in only one (1.06%) isolate. blaVIM, blaIMP and blaGES were not detected in any of the tested isolates. Conclusions: The widespread of carbapenem-resistant Klebsiella pneumoniae represents a major problem in health care settings. A significant association between certain virulence factors and carbapenemase-encoding genes was observed. Antibiotic stewardship programs and infection control policies should be effectively implemented especially in hospitals to limit the spread of such highly virulent pathogens. [ABSTRACT FROM AUTHOR]

Classification of pathogenic E. coli has been focused either in mammalian host or infection site, which offers limited resolution. This review presents a comprehensive framework for classifying all E. coli branches within a single, unifying figure. This approach integrates established methods based on virulence factors, serotypes and clinical syndromes, offering a more nuanced and informative perspective on E. coli pathogenicity. The presence of the LEE island in pathogenic E. coli is a key genetic marker differentiating EHEC from STEC strains. The coexistence of stx and eae genes within the bacterial genome is a primary characteristic used to distinguish STEC from other pathogenic E. coli strains. The presence of the inv plasmid, Afa/Dr adhesins, CFA-CS-LT-ST and EAST1 are key distinguishing features for identifying pathogenic E. coli strains belonging to EIEC, DAEC, ETEC and EAEC pathotypes respectively. Food microbiological criteria differentiate pathogenic E. coli in food matrices. 'Zero-tolerance' applies to most ready-to-eat (RTE) foods due to high illness risk. Non-RTE foods' roles may allow limited E. coli presence, which expose consumers to potential risk; particularly from the concerning Shiga toxin-producing E. coli (STEC) strains, which can lead to life-threatening complications in humans, including haemolytic uremic syndrome (HUS) and even death in susceptible individuals. These findings suggest that decision-makers should consider incorporating the separate detection of STEC serotypes into food microbiological criteria, in addition to existing enumeration methods. Contamination of STEC is mainly linked to food consumption, therefore, outbreaks of E. coli STEC has been reviewed here and showed a link also to water as a potential contamination route. Since their discovery in 1982, over 39,787 STEC cases associated with 1,343 outbreaks have been documented. The majority of these outbreaks occurred in the Americas, followed by Europe, Asia and Africa. The most common serotypes identified among the outbreaks were O157, the 'Big Six' (O26, O45, O103, O111, O121, and O145), and other serotypes such as O55, O80, O101, O104, O116, O165, O174 and O183. This review provides valuable insights into the most prevalent serotypes implicated in STEC outbreaks and identifies gaps in microbiological criteria, particularly for E. coli non-O157 and non-Big Six serotypes. [ABSTRACT FROM AUTHOR]

Introduction: Pneumocystis jirovecii pneumonia (PJP) is a life-threatening infection in immunocompromised individuals. Immune checkpoint inhibitor (ICI) has brought significant survival benefit in lung cancer patients. Although the few studies showed there was high mortality in PJP patients with ICI use, these studies had no comparative control groups. Methods: A retrospective study was conducted to compare the mortality in PJP patients with lung cancer between those treated with ICI and a concurrent control group treated without ICI. Results: A total number of 20 non-human immunodeficiency virus (HIV) patientswith confirmed PJP and co-existing lung cancer were included in the current study, and classified into ICI group (n=9) and non-ICI group (n=11). There was a clear trend to a shorter onset of PJP in ICI group than non-ICI group (118.9 ± 60.9 vs 253.0 ± 185.1 days), although without statistical significance (p=0.053). Bronchoscopic alveolar lavage fluid were collected from all patients and used to identify Pneumocystis jirovecii. In both groups, metagenomics next-generation sequencing (mNGS) were the most used diagnostic techniques. Within 28 days after the onset of PJP, mortality was significantly higher in the ICI group than non-ICI group (33.3% vs 0, p=0.042) Conclusion: Lung cancer patients with ICI use had a higher mortality rate after PJP infection than patients without ICI use. Prospective studies with larger sample size and a multi-center design are warranted to further verify the present results. [ABSTRACT FROM AUTHOR]

Background: Residents of rural areas have poorer health status, less healthy behaviours and higher mortality than urban dwellers, issues which are commonly addressed in primary care. Strengthening primary care may be an important tool to improve the health status of rural populations. Objective: Synthesize and categorize studies that examine interventions to improve rural primary care. Eligibility criteria: Experimental or observational studies published between January 1, 1996 and December 2022 that include an historical or concurrent control comparison. Sources of evidence: Pubmed, CINAHL, Cochrane Library, Embase. Charting methods: We extracted and charted data by broad category (quality, access and efficiency), study design, country of origin, publication year, aim, health condition and type of intervention studied. We assigned multiple categories to a study where relevant. Results: 372 papers met our inclusion criteria, divided among quality (82%), access (20%) and efficiency (13%) categories. A majority of papers were completed in the USA (40%), Australia (15%), China (7%) or Canada (6%). 35 (9%) papers came from countries in Africa. The most common study design was an uncontrolled before-and-after comparison (32%) and only 24% of studies used randomized designs. The number of publications each year has increased markedly over the study period from 1-2/year in 1997–99 to a peak of 49 papers in 2017. Conclusions: Despite substantial inequity in health outcomes associated with rural living, very little attention is paid to rural primary care in the scientific literature. Very few studies of rural primary care use randomized designs. [ABSTRACT FROM AUTHOR]

Background: During the COVID619 pandemic, hospitals implemented several infection control measures that could affect the quality of insertion and management of peripheral intravenous catheters $PIVCs). Pre-pandemic studies found a high rate of PIVC complications, but no studies to date have assessed the quality during the pandemic period. Objective: This prospective study aimed to investigate the effect of the pandemic on PIVC management and care. Method: Data were collected from adult patients $ [ABSTRACT FROM AUTHOR]

Escherichia coli can harbor a broad repertoire of virulence and antimicrobial resistance (AMR) genes, which can be exchanged across the human gastrointestinal microflora, thus posing a public health risk. In this study, 6 batches of artisanal soft cheese and a 6-month ripened fermented dried sausage were investigated to assess the occurrence, phylogeny, and genomic traits (AMR, virulence, and mobilome) of E. coli. 30 and 3 strains isolated from salami and cheese food chains, respectively, were confirmed as E. coli by whole genome sequencing. The accumulation of single nucleotide polymorphism differences within small clusters of strains encompassing batches or processing stages, combined with high serotype and phylogroup diversity, suggested the occurrence of different contamination phenomena among the facilities. A total of 8 isolates harbored plasmid-mediated resistance genes, including one cheese strain that carried an IncQ1 plasmid carrying AMR determinants to macrolides [mph(B)], sulfonamides (sul1, sul2), trimethoprim (dfrA1), and aminoglycosides [aph(3")-Ib and aph(6)-Id]. A pool of virulence-associated genes in the class of adhesion, colonization, iron uptake, and toxins, putative ColV-positive iron uptake systems sit, iro, or iuc (8 salami and 2 cheese), plasmid-encoded hemolysin operon hlyABCD (one salami), and potential atypical enteropathogenic E. coli (3 salami environment) were reported. Overall, our findings underscore the importance of routine surveillance of E. coli in the artisanal food chain to prevent the dissemination of AMR and virulence. [ABSTRACT FROM AUTHOR]

Purpose: The recent epidemiology of Pneumocystis pneumonia (PCP) requiring intensive care unit (ICU) admission and the associated spectrum of immunocompromising conditions are poorly described. Methods: We analyzed all adult PCP cases admitted to French ICUs via the French medical database system (PMSI), over the period from 2013 to 2019. Results: French ICUs admitted a total of 4055 adult patients with PCP. Among all hospitalized PCP cases, the proportion requiring ICU admission increased from 17.8 in 2014 to 21.3% in 2019 (P < 0.001). The incidence of severe PCP rose from 0.85 in 2013 to 1.32/100,000 adult inhabitants in 2019 (P < 0.0001), primarily due to the proportion of HIV-negative patients that increased from 60.6% to 74.4% (P < 0.0001). Meanwhile, the annual number of severe PCP cases among patients with HIV infection remained stable over the years. In-hospital mortality of severe PCP cases was 28.5% in patients with HIV infection and 49.7% in patients without. Multivariable logistic analysis showed that patients with HIV infection had a lower adjusted risk of death than patients without HIV infection (Odds Ratio [OR]: 0.30, 95% confidence interval [95CI]: 0.17–0.55). Comorbidities or conditions strongly associated with hospital mortality included the patient's age, Simplified Acute Physiologic Score II, congestive heart failure, coagulopathy, solid organ cancer, and cirrhosis. A vast array of autoimmune inflammatory diseases affected 19.9% of HIV-negative patients. Conclusions: The number of PCP cases requiring ICU admission in France has risen sharply. While the yearly count of severe PCP cases in HIV-infected patients has remained steady, this rise predominantly affects cancer patients, with a recent surge observed in patients with autoimmune inflammatory diseases, affecting one in five individuals. [ABSTRACT FROM AUTHOR]

Introduction: Pneumocystis jirovecii pneumonia (PJP) is a well-known and frequent opportunistic infection in HIV patients. However, there has been an increase in the number of reports of PJP in other immunosuppressed patients with autoimmune inflammatory disorders or because of chemotherapy and high doses of steroids, especially when used in combination as part of immunosuppressive therapy. Objective: Despite the increasing importance of PJP in non-HIV patients, there is a lack of comprehensive and updated information on the epidemiology, pathogenesis, diagnosis, microbiology, treatments, and prophylaxis of this infection in this population. Therefore, the objective of this systematic review is to synthesize information on these aspects, from a perspective of evidence-based medicine. Methods: The protocol is prepared following the preferred reporting items for systematic reviews and meta-analyses (PRISMA-P) guidelines. We will perform a systematic review of literature published between January 2010 and July 2023, using the databases PubMed, Google Scholar, ScienceDirect, and Web of Science. In addition, manual searches will be carried out through related articles, and references to included articles. The main findings and clinical outcomes were extracted from all the eligible studies with a standardized instrument. Two authors will independently screen titles and abstracts, review full texts, and collect data. Disagreements will be resolved by discussion, and a third reviewer will decide if there is no consensus. We will synthesize the results using a narrative or a meta-analytic approach, depending on the heterogeneity of the studies. Expected results: It is expected that this systematic review will provide a comprehensive and up-to-date overview of the state-of-the-art of PJP in non-HIV patients. Furthermore, the study will highlight possible gaps in knowledge that should be addressed through new research. Conclusions: Here, we present the protocol for a systematic review which will consider all existing evidence from peer-reviewed publication sources relevant to the primary and secondary outcomes related to diagnosing and managing PJP in non-HIV patients. [ABSTRACT FROM AUTHOR]

Background: During the COVID619 pandemic, hospitals implemented several infection control measures that could affect the quality of insertion and management of peripheral intravenous catheters $PIVCs). Pre-pandemic studies found a high rate of PIVC complications, but no studies to date have assessed the quality during the pandemic period. Objective: This prospective study aimed to investigate the effect of the pandemic on PIVC management and care. Method: Data were collected from adult patients $_18 years) at a university hospital in Norway during a three-week period in February 2020 (pre-pandemic: PP group) and a three-week period in October 2020 (pandemic: P group). The primary outcome measure was PIVC quality as determined by the validated PIVC Mini Questionnaire $PIVC-miniQ%, which consists of 16 items relating to deviations from best practice. Results: The study included 483 PIVCs and 413 patients. Of these, 238 PIVCs $49.3%% were collected in the PP group and 245 $50.7%% in the P group. In the PP group, 41.8% of the PIVCs were 18 gauge (green PIVC% or larger, compared to 53.3% in the P group. The median PIVC-miniQ score was 2 in both groups, with a range of 0710 in the PP group and 078 in the P group. Improved quality in terms of fewer patients reporting pain was registered in the P group $14.3% compared to 6.7%%, and 36.3% had blood in the IV line in the PP group, compared to 26.5% in the P group. However, a poorer quality was observed in the P group for the PIVC-miniQ items 'purulence' $0% in the PP group compared to 6% in the P group) and 'loose dressing' $15.2% in the PP group compared to 24.9% in the P group). Documentation of PIVC insertion and indication was equally insufficient in both groups (p = 0.857%. Conclusion: Although some differences were observed at item level, the PIVC quality as measured by the PIVC-miniQ total score remained unchanged during the pandemic. Given the low workload of our hospital during the pandemic, it is a paradox that the PIVC care did not improve. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) B infections remain a primary global health concern. The immunopathology of the infection, specifically the interactions between HBV and the host immune system, remains somewhat unknown. It has been discovered that innate immune reactions are vital in eliminating HBV. Toll-like receptors (TLRs) are an essential category of proteins that detect pathogen-associated molecular patterns (PAMPs). They begin pathways of intracellular signals to stimulate pro-inflammatory and anti-inflammatory cytokines, thus forming adaptive immune reactions. HBV TLRs include TLR2, TLR3, TLR4, TLR7 and TLR9. Each TLR has its particular molecule to recognize; various TLRs impact HBV and play distinct roles in the pathogenesis of the disease. TLR gene polymorphisms may have an advantageous or disadvantageous efficacy on HBV infection, and some single nucleotide polymorphisms (SNPs) can influence the progression or prognosis of infection. Additionally, it has been discovered that similar SNPs in TLR genes might have varied effects on distinct populations due to stress, diet, and external physical variables. In addition, activation of TLR-interceded signaling pathways could suppress HBV replication and increase HBV-particular T-cell and B-cell reactions. By identifying these associated polymorphisms, we can efficiently advance the immune efficacy of vaccines. Additionally, this will enhance our capability to forecast the danger of HBV infection or the threat of dependent liver disease development via several TLR SNPs, thus playing a role in the inhibition, monitoring, and even treatment guidance for HBV infection. This review will show TLR polymorphisms, their influence on TLR signaling, and their associations with HBV diseases. [ABSTRACT FROM AUTHOR]

Objectives: Cytomegalovirus (CMV) is frequently detected in lung and/or blood samples of patients with Pneumocystis jirovecii pneumonia (PJP), although this co-detection is not precisely understood. We aimed to determine whether PJP was more severe in case of CMV detection. Methods: We retrospectively included all patients with a diagnosis of PJP between 2009 and 2020 in our centre and with a measure of CMV viral load in blood and/or bronchoalveolar lavage (BAL). PJP severity was assessed by the requirement for intensive care unit (ICU) admission. Results: The median age of the 249 patients was 63 [IQR: 53–73] years. The main conditions were haematological malignancies (44.2%), solid organ transplantations (16.5%), and solid organ cancers (8.8%). Overall, 36.5% patients were admitted to ICU. CMV was detected in BAL in 57/227 patients; the 37 patients with viral load ≥3 log copies/mL were more frequently admitted to ICU (78.4% vs 28.4%, p<0.001). CMV was also detected in blood in 57/194 patients; the 48 patients with viral load ≥3 log copies/mL were more frequently admitted to ICU (68.7% vs 29.4%, p<0.001). ICU admission rate was found to increase with each log of BAL CMV viral load and each log of blood CMV viral load. Conclusions: PJP is more severe in the case of concomitant CMV detection. This may reflect either the deleterious role of CMV itself, which may require antiviral therapy, or the fact that patients with CMV reactivation are even more immunocompromised. [ABSTRACT FROM AUTHOR]

Background: The repercussions of the syphilis epidemic differ according to populations. Identifying and acknowledging the differences and specificities of populations is fundamental in the design and implementation of policies aimed at assisting the groups most vulnerable to syphilis. Objective: To estimate the prevalence of antibodies against Treponema pallidum and associated vulnerability factors among riverside populations of a capital city in the Brazilian Amazon. Methods: Cross-sectional study was conducted among residents of the periurban islands in Belém, northern Brazil, from August 2020 to January 2021. The inclusion criterion was being a resident of the riverside communities of the Combú Environmental Protection Area, aged 18 years or over. The participants responded to questionnaire and were tested for syphilis using rapid test. Data were analyzed using multiple logistic regression by Minitab version 20® software. Results: Overall, a total of 325 riverine were included. Age varied from 18 to 91 years (average 40 years). Prevalence of markers for syphilis was 5.9% (95% CI: 3.3%-8.4%). The multiple regression showed that as age increases, the chances of having syphilis also increase (p = 0.001; aOR: 1.04) and riverside dwellers with more than one sexual partner in the last 6 months had more than four chances of having syphilis compared to people who had only one sexual partner (p = 0.007; aOR: 4.20). Conclusion: Syphilis circulates among traditional populations in the Amazon and is associated with factors of social and individual vulnerability. [ABSTRACT FROM AUTHOR]

Excluding children with Shiga toxin-producing Escherichia coli (STEC) from childcare until microbiologically clear of the pathogen, disrupts families, education, and earnings. Since PCR introduction, non-O157 STEC serotype detections in England have increased. We examined shedding duration by serotype and transmission risk, to guide exclusion advice. We investigated STEC cases aged <6 years, residing in England and attending childcare, with diarrhoea onset or sample date from 31 March 2018 to 30 March 2022. Duration of shedding was the interval between date of onset or date first positive specimen and earliest available negative specimen date. Transmission risk was estimated from proportions with secondary cases in settings attended by infectious cases. There were 367 cases (STEC O157 n  = 243, 66.2%; STEC non-O157 n  = 124, 33.8%). Median shedding duration was 32 days (IQR 20–44) with no significant difference between O157 and non-O157; 2% (n  = 6) of cases shed for ≥100 days. Duration of shedding was reduced by 17% (95% CI 4–29) among cases reporting bloody diarrhoea. Sixteen settings underwent screening; four had secondary cases (close contacts' secondary transmission rate = 13%). Shedding duration estimates were consistent with previous studies (median 31 days, IQR 17–41). Findings do not warrant guidance changes regarding exclusion and supervised return of prolonged shedders, despite serotype changes. [ABSTRACT FROM AUTHOR]

The quorum sensing two-component system (TCS) QseBC has been linked to virulence, motility and metabolism regulation in multiple Gram-negative pathogens, including Enterohaemorrhagic Escherichia coli (EHEC), Uropathogenic E. coli (UPEC) and Salmonella enterica. In EHEC, the sensor histidine kinase (HK) QseC detects the quorum sensing signalling molecule AI-3 and also acts as an adrenergic sensor binding host epinephrine and norepinephrine. Downstream changes in gene expression are mediated by phosphorylation of its cognate response regulator (RR) QseB, and ʻcross-talksʼ with non-cognate regulators KdpE and QseF to activate motility and virulence. In UPEC, cross-talk between QseBC and TCS PmrAB is crucial in the regulation and phosphorylation of QseB RR that acts as a repressor of multiple pathways, including motility. Here, we investigated QseBC regulation of motility in the atypical Enteropathogenic E. coli (EPEC) strain O125ac:H6, causative agent of persistent diarrhoea in children, and its possible cross-talk with the KdpDE and PmrAB TCS. We showed that in EPEC QseB acts as a repressor of genes involved in motility, virulence and stress response, and in absence of QseC HK, QseB is likely activated by the non-cognate PmrB HK, similarly to UPEC. We show that in absence of QseC, phosphorylated QseB activates its own expression, and is responsible for the low motility phenotypes seen in a QseC deletion mutant. Furthermore, we showed that KdpD HK regulates motility in an independent manner to QseBC and through a third unidentified party different to its own response regulator KdpE. We showed that PmrAB has a role in iron adaptation independent to QseBC. Finally, we showed that QseB is the responsible for activation of colistin and polymyxin B resistance genes while PmrA RR acts by preventing QseB activation of these resistance genes. Author summary: Enteropathogenic Escherichia coli (EPEC) is a human pathogen and the leading cause of diarrhoea in children under 5 years in low-income countries. EPEC, and specially the subgroup denominated atypical EPEC, has been associated with community-acquired persistent diarrhoea and also is an important agent of post-weaning diarrhoea in young piglets. Two-component systems (TCS) are signalling system used by bacteria to sense and adapt to different stimuli. Bacteria use TCS to detect host signals as cues to exert virulence in their preferred niche. QseBC is a TCS that has been linked to regulation of motility and virulence in other pathogenic E. coli. In this study we broaden our understanding of QseBC TCS and its role in regulating virulence traits such as motility in atypical EPEC. We also investigate its capabilities to interact with other TCS, named KdpDE and PmrAB, and how these interactions are responsible for regulation of motility and resistance to antimicrobials such as colistin. [ABSTRACT FROM AUTHOR]

Purpose: Culture-negative urine specimens can be rapidly screened by urine flow cytometry (UFC), while low positive predictive value (PPV) limits the clinical application. We explored the factors associated with a low PPV. Methods: A total of 5095 urine specimens were analyzed with UFC and culture. Diagnostic performance of leukocytes, bacteria, and BACT-info flags was evaluated by sensitivity, specificity, PPV, and negative predictive value (NPV). The association of contaminated culture and squamous epithelial cell count and BACT-info flag was performed by logistic regression analysis. Results: The NPVs of parallel combination of bacteria and leucocytes were 98.9% in males and 97.9% in females, and PPVs of serial combination were 86.6% and 77.8% in men and women, respectively. The PPV of Gram-negative flag was higher than that of Gram-positive flag. The proportions of contamination in the urine culture results of false positive specimens were 86.9% in males and 98.5% in females at the cutoff points of the serial combination, and these parameters were 53.2% in males and 85.6% in females for the Gram-positive flag. There was a statistically significant association between contaminated cultures and squamous epithelial cells count in females, but not in males. Associations between contaminated cultures and Gram-positive flags or Gram-pos/-neg flags were statistically significant, but there was no association between contaminated cultures and Gram-negative flags. Conclusions: A serial combination of leukocytes and bacteria may maximize PPV in the diagnosis of bacterial urinary tract infection by urine flow cytometry, and contamination is the main reason for a low PPV. [ABSTRACT FROM AUTHOR]

Background: The spread and adaptation of horseflies to new habitats, driven by global climate change, threatens not only animal health but also human well-being. Objective: This article addresses the significant health risks posed by horseflies, which are known carriers of multiple pathogens causing up to 25 different infectious, parasitic, and viral diseases, including anthrax, tularemia, leptospirosis, and anaplasmosis. Methodology: The study provided an overview based on an extensive literature review from 1929 to 2022, analyzing both Russian and English publications. Results: The 2011 tularemia outbreak in Norway, linked to lemming population surges, and the higher susceptibility among men in Slovakia's annual tularemia cases highlight the role of animal reservoirs and gender in disease transmission. Leptospirosis, prevalent globally except in cold regions, is influenced by climate events, with significant public health impacts observed in various regions, including Russia and the Philippines following natural disasters. Anaplasmosis, transmitted by insects and ticks and more prevalent in warmer months, remains under-researched, with its rising threat exemplified by the growing ixodes tick population in Belarus. Conclusion: In conclusion, understanding the epidemiology and sources of these diseases, along with recognizing the environmental and anthropogenic factors that influence their transmission, is vital. The study underscores the importance of ongoing surveillance, research, and preventive measures to mitigate the impact of these infectious diseases on public health. [ABSTRACT FROM AUTHOR]

Aims: Intravenous amiodarone is an irritant of peripheral blood vessels with phlebitis as an adverse effect. The aims were to determine the incidence of intravenous amiodarone-induced phlebitis, to describe adherence to a clinical practice guideline, and to determine how characteristics were distributed between those with and without phlebitis. Methods and results: A prospective observational study was conducted. Adult patients treated with amiodarone through a peripheral intravenous catheter (PIVC) or a central venous catheter were included. PIVC characteristics were measured using the PIVC mini questionnaire. Patients with ≥two signs of phlebitis were categorized as having phlebitis. Adherence to the clinical practice guideline was registered on a standard abstract sheet. Data were collected from the amiodarone start-up to 2 days after the amiodarone was discontinued. In total, 124 patients with amiodarone infusions were observed, of which 69% were administered via a PIVC. The phlebitis rate was 44%. Fifty-three per cent developed amiodarone-induced phlebitis during the infusion phase, while 47% presented phlebitis during the post-infusion phase. The three most observed signs or symptoms of phlebitis were redness (87%), pain (81%), and swelling (71%). The most commonly used PIVC site was the elbow, and 35% of the PIVCs were large (18 gauge), which was the last preferred site and size according to the clinical practice guideline. Conclusion: A large proportion of the patients developed amiodarone-induced phlebitis. The adherence to the clinical practice guideline was not optimal according to the PIVC recommendations. Prevention of amiodarone-induced phlebitis should have high priority to reduce patient harm. Graphical Abstract [ABSTRACT FROM AUTHOR]

Purpose: To detect the possible safety signal of purine antimetabolites associated with Pneumocystis jirovecii pneumonia through disproportionality analysis in the FDA Adverse Event Reporting System (FAERS) Database. Methods: A case/non‐case retrospective disproportionality analysis was performed in the publicly available FAERS database using AERSmine (2004Q1–2021Q3). Four models were developed to explore the signal strength of PAs among different populations with possible confounding factors. Reporting odds ratio (ROR) and Proportional reporting ratio (PRR) was used as the data mining algorithm for the analysis. A value of ROR‐1.96SE > 1 and PRR ≥ 2 with an associated X2 value of 4 or more was considered the threshold for a signal. Results: A total of 7073 reports associated with Pneumocystis jirovecii pneumonia were present in the database, of which 899 reports were associated with purine antimetabolites. A crude signal strength of ROR 15.76(14.70–16.91) was obtained for purine antimetabolites associated PJP, with the highest signal strength reported with fludarabine and thioguanine [ROR 19.63(17.42–22.13); 19.45(13.21–28.63)]. Stratifying the cases based on autoimmune disorders and the cancer population revealed an ROR of 3.33(2.46–4.50) and 2.93(2.26–3.79) respectively. The highest risk of PJP with use of PAs was observed amongst children with a higher risk of nearly 2 times than the adult population [ROR 11.57(9.16–14.62)]. Conclusions: Our study provided evidence on the occurrence of PJP with the use of purine antimetabolites among the autoimmune and cancer population. We identified signals for PJP with azathioprine, mercaptopurine, thioguanine, cladribine, fludarabine, and clofarabine. More research with a superior epidemiological study design of a defined population is required to validate these findings. [ABSTRACT FROM AUTHOR]

The imbalance of immune response plays a crucial role in the development of diseases, including glioblastoma. It is essential to comprehend how the innate immune system detects tumors and pathogens. Endosomal and cytoplasmic sensors can identify diverse cancer cell antigens, triggering the production of type I interferon and pro-inflammatory cytokines. This, in turn, stimulates interferon stimulating genes, enhancing the presentation of cancer antigens, and promoting T cell recognition and destruction of cancer cells. While RNA and DNA sensing of tumors and pathogens typically involve different receptors and adapters, their interaction can activate adaptive immune response mechanisms. This review highlights the similarity in RNA and DNA sensing mechanisms in the innate immunity of both tumors and pathogens. The aim is to enhance the antitumor innate immune response, identify regions of the tumor that are not responsive to treatment, and explore new targets to improve the response to conventional tumor therapy and immunotherapy. [ABSTRACT FROM AUTHOR]

The female genital ulcer is a manifestation of many diseases, which may vary depending on the etiology, disease duration, age, and host immunity. A middle-aged (40–50 years) woman had a 4-month history of vaginal bleeding. The results of syphilis, herpes, the cervical cancer, tuberculosis, and fungi or acute cervical inflammation caused by Chlamydia trachomatis and Mycoplasma hominis were negative through the blood test and the biopsy. Cervical discharge culture revealed positive for group B Streptococcus and bacterial vaginosis. The patient was treated with oral antibiotics for 7 days. One month later, repeat colposcopy revealed a smooth cervix and complete ulcer disappearance, while cervical discharge culture retested no group B Streptococcus and bacterial vaginosis. The patient was diagnosed with cervical ulcer. Complete medical history taking and bacterial culture of cervical discharge are important for identifying the etiology of the cervical ulcer and deciding the appropriate treatment for the disease. [ABSTRACT FROM AUTHOR]

Background: Diarrhea is a serious health problem in children, with the highest mortality rate in sub-Saharan Africa. Diarrheagenic Escherichia coli (DEC) is among the major bacterial causes of diarrhea in children under age five. The present study aims to determine molecular epidemiology and antimicrobial resistance profiles of DEC and identify contributing factors for acquisition among children under age five in Central Ethiopia. Methods: A health facility-centered cross-sectional study was conducted in Addis Ababa and Debre Berhan, Ethiopia, from December 2020 to August 2021. A total of 476 specimens, 391 from diarrheic and 85 from non-diarrheic children under age five were collected. Bacterial isolation and identification, antimicrobial susceptibility, and pathotype determination using polymerase chain reaction (PCR) were done. Results: Of the 476 specimens analyzed, 89.9% (428/476) were positive for E. coli, of which 183 were positive for one or more genes coding DEC pathotypes. The overall prevalence of the DEC pathotype was 38.2% (183/476). The predominant DEC pathotype was enteroaggregative E. coli (EAEC) (41.5%, 76/183), followed by enterotoxigenic E. coli (21.3%, 39/183), enteropathogenic E. coli (15.3%, 28/183), enteroinvasive E. coli (12.6%, 23/183), hybrid strains (7.1%, 13/183), Shiga toxin-producing E. coli (1.6%, 3/183), and diffusely-adherent E. coli (0.6%, 1/183). DEC was detected in 40.7% (159/391) of diarrheic and 28.2% (24/85) in non-diarrheic children (p = 0.020). The majority of the DEC pathotypes were resistant to ampicillin (95.1%, 174/183) and tetracycline (91.3%, 167/183). A higher rate of resistance to trimethoprim-sulfamethoxazole (58%, 44/76), ciprofloxacin (22%, 17/76), ceftazidime and cefotaxime (20%, 15/76) was seen among EAEC pathotypes. Multidrug resistance (MDR) was detected in 43.2% (79/183) of the pathotypes, whereas extended spectrum ß-lactamase and carbapenemase producers were 16.4% (30/183) and 2.2% (4/183), respectively. Conclusion: All six common DEC pathotypes that have the potential to cause severe diarrheal outbreaks were found in children in the study area; the dominant one being EAEC with a high rate of MDR. [ABSTRACT FROM AUTHOR]

Mycobacterium avium complex (MAC) houses a group of non-tuberculous mycobacteria causing pulmonary and disseminated infections. They are accountable for nodular bronchiectatic and fibrocavitary lung diseases in humans, Johne’s disease in ruminants, and respiratory diseases in birds. MAC infections pose challenges, owing to antibiotic resistance, prolonged therapy with antibiotic combinations, side effects, and risk of reinfections. Our objective was to summarize the outcome of computational research on the bacteria in MAC. This aimed to advance our understanding of characteristics, pathogenicity, and transmission dynamics to control infections. We incorporated information from the research on genomes, microbiomes, phylogeny, transcriptomes, proteomes, antibiotic resistance, and vaccine/drug target development to enhance our knowledge. It illuminated the significance of computational studies in distinguishing MAC species/subspecies and recognizing: virulence factors, lineage-specific markers, and transmission clusters. Moreover, it assisted in understanding: genomic diversity, resistance patterns, impact of polymorphisms in disease susceptibility, and taxa-induced dysbiosis in microbiomes. Additionally, this work highlighted the outcome of bioinformatic studies in predicting suitable vaccine epitopes, and novel drug targets to combat MAC infections. Bioinformatic research on bacteria within MAC has contributed to a deeper insight into the pathogens. These would facilitate better diagnosis, improved: therapeutic strategies, patient-specific surveillance, and community-level awareness. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus (DM2) and osteoporosis (OP) are currently the two most significant causes of mortality and morbidity in older adults, according to clinical evidence. The intrinsic link between them is yet unknown, despite reports of their coexistence. By utilizing the two-sample Mendelian randomization (MR) approach, we sought to evaluate the causal impact of DM2 on OP. Methods: The aggregate data of the whole gene-wide association study (GWAS) were analyzed. A two-sample MR analysis was performed using single-nucleotide polymorphisms (SNPs), which are strongly associated with DM2, as instrumental variables (IVs) to evaluate the causal analysis of DM2 on OP risk with OR values, using inverse variance weighting, MR-egger regression, and weighted median methods, respectively. Result: A total of 38 single nucleotide polymorphisms were included as tool variables. According to the results of inverse variance-weighted (IVW), we found that there was a causal relationship between DM2 and OP, in which DM2 had a protective effect on OP. For each additional case of DM2, there is a 0.15% decrease in the odds of developing OP (OR = 0.9985;95%confidence interval:0.9974,0.9995; P value = 0.0056). There was no evidence that the observed causal effect between DM2 and the risk of OP was affected by genetic pleiotropy (P = 0.299). Using Cochran Q statistics and MR-Egger regression in the IVW approach, the heterogeneity was calculated; P > 0.05 shows that there is a significant amount of heterogeneity. Conclusion: A causal link between DM2 and OP was established by MR analysis, which also revealed that DM2 decreased the occurrence of OP. [ABSTRACT FROM AUTHOR]

Background: To address knowledge gaps regarding diarrheagenic Escherichia coli (DEC) in Africa, we assessed the clinical and epidemiological features of enteroaggregative E. coli (EAEC), enteropathogenic E. coli (EPEC), and Shiga toxin–producing E. coli (STEC) positive children with moderate-to-severe diarrhea (MSD) in Mali, The Gambia, and Kenya. Methods: Between May 2015 and July 2018, children aged 0–59 months with medically attended MSD and matched controls without diarrhea were enrolled. Stools were tested conventionally using culture and multiplex polymerase chain reaction (PCR), and by quantitative PCR (qPCR). We assessed DEC detection by site, age, clinical characteristics, and enteric coinfection. Results: Among 4840 children with MSD and 6213 matched controls enrolled, 4836 cases and 1 control per case were tested using qPCR. Of the DEC detected with TAC, 61.1% were EAEC, 25.3% atypical EPEC (aEPEC), 22.4% typical EPEC (tEPEC), and 7.2% STEC. Detection was higher in controls than in MSD cases for EAEC (63.9% vs 58.3%, P <.01), aEPEC (27.3% vs 23.3%, P <.01), and STEC (9.3% vs 5.1%, P <.01). EAEC and tEPEC were more frequent in children aged <23 months, aEPEC was similar across age strata, and STEC increased with age. No association between nutritional status at follow-up and DEC pathotypes was found. DEC coinfection with Shigella/enteroinvasive E. coli was more common among cases (P <.01). Conclusions: No significant association was detected between EAEC, tEPEC, aEPEC, or STEC and MSD using either conventional assay or TAC. Genomic analysis may provide a better definition of the virulence factors associated with diarrheal disease. [ABSTRACT FROM AUTHOR]

Purpose: The incidence of Pneumocystis pneumonia (PCP) in patients without human immunodeficiency virus (HIV) has been increasing. In this study, we aimed to investigate the metabolic changes in Pneumocystis infection and the metabolic abnormalities in B-cell-activating factor receptor (BAFF-R)-deficient mice with Pneumocystis infection. Methods: The important function of B cells during Pneumocystis infection is increasingly recognized. In this study, a Pneumocystis-infected mouse model was constructed in BAFF-R–/– mice and wild-type (WT) mice. Lungs of uninfected WT C57BL/6, WT Pneumocystis-infected, and BAFF-R–/–Pneumocystis-infected mice were used for metabolomic analyses to compare the metabolomic profiles among the groups, with the aim of exploring the metabolic influence of Pneumocystis infection and the influence of mature B-cell deficiency during infection. Results: The results indicated that many metabolites, mainly lipids and lipid-like molecules, were dysregulated in Pneumocystis-infected WT mice compared with uninfected WT C57BL/6 mice. The data also demonstrated significant changes in tryptophan metabolism, and the expression levels of key enzymes of tryptophan metabolism, such as indoleamine 2,3-dioxygenase 1 (IDO1), were significantly upregulated. In addition, B-cell development and function might be associated with lipid metabolism. We found a lower level of alitretinoin and the abnormalities of fatty acid metabolism in BAFF-R–/–Pneumocystis-infected mice. The mRNA levels of enzymes associated with fatty acid metabolism in the lung were upregulated in BAFF-R–/–Pneumocystis-infected mice and positively correlated with the level of IL17A, thus suggesting that the abnormalities of fatty acid metabolism may be associated with greater inflammatory cell infiltration in the lung tissue of BAFF-R–/–Pneumocystis-infected mice compared with the WT Pneumocystis-infected mice. Conclusion: Our data revealed the variability of metabolites in Pneumocystis-infected mice, suggesting that the metabolism plays a vital role in the immune response to Pneumocystis infection. [ABSTRACT FROM AUTHOR]

Background: Hemolytic uremic syndrome (HUS) is characterized by microangiopathic hemolysis, thrombocytopenia, and thrombus formation leading to tissue injury. HUS is classified according to its etiology as post-diarrheal or atypical HUS. Differential diagnosis of both entities continues to be a challenge for pediatric physicians. Methods: The aim was to improve the rapid etiological diagnosis of post-diarrheal HUS cases based on the detection of Shiga toxin (Stx)-producing Escherichia coli (STEC) infection by screening of stx1/stx2 and rfbO157 in cultured stools by multiplex PCR, and the additional detection of anti-lipopolysaccharide (anti-LPS) O157, O145, and O121 antibodies by Glyco-iELISA test. In addition, we studied patients' relatives to detect circulating pathogenic strains that could contribute to HUS diagnosis and/or lead to the implementation of measures to prevent dissemination of familial outbreaks. This study describes the diagnosis of 31 HUS patients admitted to Hospital Municipal de Niños Prof Dr Ramón Exeni during the 2017–2020 period. Results: Stool PCR confirmed the diagnosis of STEC associated with HUS in 38.7% of patients (12/31), while anti-LPS serology did in 88.9% (24/27). In those patients in which both methods were carried out (n = 27), a strong association between the results obtained was found. We found that 30.4% of HUS patients had at least one relative positive for STEC. Conclusions: We could identify 96.3% (26/27) of HUS cases as secondary to STEC infections when both methods (genotyping and serology) were used. The results demonstrated a high circulation of STEC in HUS families and the prevalence of the STEC O157 serotype (83%) in our pediatric cohort. A higher-resolution version of the Graphical abstract is available as Supplementary information. [ABSTRACT FROM AUTHOR]

Currently, atovaquone is not recommended for treating severe Pneumocystis jirovecii pneumonia (PCP) due to insufficient evidence in clinical studies. This report describes a case of severe PCP in a human immunodeficiency virus (HIV)-negative immunosuppressed patient who was successfully treated with oral atovaquone and corticosteroids. A 63-year-old Japanese woman complained of fever and dyspnea for 3 days. She had been treated with oral prednisolone (30 mg/day) for interstitial pneumonia for 3 months without PCP prophylaxis. Although we could not confirm P. jirovecii from the respiratory specimen, a diagnosis of PCP was indicated by marked elevation of serum beta-D-glucan levels and bilateral ground-glass opacities in the lung fields. Based on the arterial blood gas test results (alveolar-arterial oxygen difference > 45 mmHg), the disease status of PCP was defined as severe. Trimethoprim-sulfamethoxazole (SXT) is the first-line drug for treating severe PCP. However, given the patient's history of SXT-induced toxic epidermal necrolysis, she was administered atovaquone instead of SXT. Her clinical symptoms and respiratory condition gradually improved, with a 3-week treatment showing a good clinical course. Previous clinical studies on atovaquone have only been conducted in HIV-positive patients with mild or moderate PCP. Accordingly, the clinical efficacy of atovaquone for severe PCP cases or PCP in HIV-negative patients remains unclear. There is a rising incidence of PCP among HIV-negative patients, given the increasing number of patients receiving immunosuppressive medications; moreover, atovaquone has less severe side effects than SXT. Therefore, there is a need for further clinical investigation to confirm the efficacy of atovaquone in cases of severe PCP, especially among HIV-negative patients. In addition, it also remains unclear whether corticosteroids are beneficial for severe PCP in non-HIV patients. Thus, the use of corticosteroids in cases of severe PCP in non-HIV patients should also be investigated. [ABSTRACT FROM AUTHOR]

The Toll-like receptors (TLRs) and interleukin-1 receptors (IL-1R) families are of paramount importance in coordinating the early immune response to pathogens. Signaling via most TLRs and IL-1Rs is mediated by the protein myeloid differentiation primary-response protein 88 (MyD88). This signaling adaptor forms the scaffold of the myddosome, a molecular platform that employs IL-1Rassociated kinase (IRAK) proteins as main players for transducing signals. These kinases are essential in controlling gene transcription by regulating myddosome assembly, stability, activity and disassembly. Additionally, IRAKs play key roles in other biologically relevant responses such as inflammasome formation and immunometabolism. Here, we summarize some of the key aspects of IRAK biology in innate immunity. [ABSTRACT FROM AUTHOR]

The polarization of macrophages to the M1 or M2 phenotype has a pivotal role in inflammatory response following myocardial ischemia/reperfusion injury. Peli1, an E3 ubiquitin ligase, is closely associated with inflammation and autoimmunity as an important regulatory protein in the Toll-like receptor signaling pathway. We aimed to explore the function of Peli1 in macrophage polarization under myocardial ischemia/reperfusion injury and elucidate the possible mechanisms. We show here that Peli1 is upregulated in peripheral blood mononuclear cells from patients with myocardial ischemia/reperfusion, which is correlated with myocardial injury and cardiac dysfunction. We also found that the proportion of M1 macrophages was reduced and myocardial infarct size was decreased, paralleling improvement of cardiac function in mice with Peli1 deletion in hematopoietic cells or macrophages. Macrophage Peli1 deletion lessened M1 polarization and reduced the migratory ability in vitro. Mechanistically, Peli1 contributed to M1 polarization by promoting K63-linked ubiquitination and nuclear translocation of IRF5. Moreover, Peli1 deficiency in macrophages reduced the apoptosis of cardiomyocytes in vivo and in vitro. Together, our study demonstrates that Peli1 deficiency in macrophages suppresses macrophage M1 polarization and alleviates myocardial ischemia/reperfusion injury by inhibiting the nuclear translocation of IRF5, which may serve as a potential intervention target for myocardial ischemia/reperfusion injury. [ABSTRACT FROM AUTHOR]

Background Recent studies have reported that reduced-dose trimethoprim-sulfamethoxazole (TMP-SMX) may be effective in the treatment of Pneumocystis jirovecii pneumonia (PJP), but data are lacking for patients with hematologic malignancies. Methods This retrospective study included all adult hematologic patients with PJP between 2013 and 2017 at 6 Swedish university hospitals. Treatment with 7.5–15 mg TMP/kg/day (reduced dose) was compared with >15–20 mg TMP/kg/day (standard dose), after correction for renal function. The primary outcome was the change in respiratory function (Δpartial pressure of oxygen [PaO2]/fraction of inspired oxygen [FiO2]) between baseline and day 8. Secondary outcomes were clinical failure and/or death at day 8 and death at day 30. Results Of a total of 113 included patients, 80 patients received reduced dose and 33 patients received standard dose. The overall 30-day mortality in the whole cohort was 14%. There were no clinically relevant differences in ΔPaO2/FiO2 at day 8 between the treatment groups, either before or after controlling for potential confounders in an adjusted regression model (−13.6 mm Hg [95% confidence interval {CI}, −56.7 to 29.5 mm Hg] and −9.4 mm Hg [95% CI, −50.5 to 31.7 mm Hg], respectively). Clinical failure and/or death at day 8 and 30-day mortality did not differ significantly between the groups (18% vs 21% and 14% vs 15%, respectively). Among patients with mild to moderate pneumonia, defined as PaO2/FiO2 >200 mm Hg, all 44 patients receiving the reduced dose were alive at day 30. Conclusions In this cohort of 113 patients with hematologic malignancies, reduced-dose TMP-SMX was effective and safe for treating mild to moderate PJP. [ABSTRACT FROM AUTHOR]

Twenty-five susceptibility loci for SARS-CoV-2 infection and/or COVID-19 disease severity have been identified in the human genome by genome-wide association studies, and the most frequently replicated genetic findings for susceptibility are genetic variants at the ABO gene locus on chromosome 9q34.2, which is supported by the association between ABO blood group distribution and COVID-19. The ABO blood group effect appears to influence a variety of disease conditions and pathophysiological mechanisms associated with COVID-19. Transmission models for SARS-CoV-2 combined with observational public health and genome-wide data from patients and controls, as well as receptor binding experiments in cell lines and human samples, indicate that there may be a reduction or slowing of infection events by up to 60% in certain ABO blood group constellations of index and contact person in the early phase of a SARS-CoV-2 outbreak. The strength of the ABO blood group effect on reducing infection rates further depends on the distribution of the ABO blood groups in the respective population and the proportion of blood group O in that population. To understand in detail the effect of ABO blood groups on COVID-19, further studies are needed in relation to different demographic characteristics, but also in relation to recent data on reinfection with new viral variants and in the context of the human microbiome. [ABSTRACT FROM AUTHOR]

Background This study was performed to determine the incidence of group B Streptococcus (GBS) disease among extremely preterm infants and assess to risk of death or neurodevelopmental impairment (NDI) at a corrected age of 18–26 months. Methods In this observational cohort study of infants enrolled in a multicenter registry, the incidence of GBS disease was assessed in infants born in 1998–2016 at 22–28 weeks' gestation and surviving for >12 hours. The composite outcome, death or NDI, was assessed in infants born in 1998–2014 at 22–26 weeks' gestation. Infection was defined as GBS isolation in blood or cerebrospinal fluid culture at ≤72 hours (early-onset disease [EOD]) or >72 hours (late-onset disease [LOD]) after birth. Using Poisson regression models, the outcome was compared in infants with GBS disease, infants infected with other pathogens, and uninfected infants. Results The incidence of GBS EOD (2.70/1000 births [95% confidence interval (CI), 2.15–3.36]) and LOD (8.47/1000 infants [7.45–9.59]) did not change significantly over time. The adjusted relative risk of death/NDI was higher among infants with GBS EOD than in those with other infections (adjusted relative risk, 1.22 [95% CI, 1.02–1.45]) and uninfected infants (1.44 [1.23–1.69]). Risk of death/NDI did not differ between infants with GBS LOD and comparator groups. GBS LOD occurred at a significantly later age than non-GBS late-onset infection. Among infants surviving >30 days, the risk of death was higher with GBS LOD (adjusted relative risk, 1.90 [95% CI, 1.36–2.67]), compared with uninfected infants. Conclusions In a cohort of extremely preterm infants, the incidence of GBS disease did not change during the study period. The increased risk of death or NDI with GBS EOD, and of death among some infants with GBS LOD, supports the need for novel preventive strategies for disease reduction. Clinical Trials Registration NCT00063063. [ABSTRACT FROM AUTHOR]

Background Group B streptococcal (GBS) infection remains one of the most significant causes of late-onset sepsis and meningitis (LOGBS) among young infants. However, transmission routes and risk factors for LOGBS are not yet fully understood. Methods We conducted systematic reviews on clinical risk factors previously reported in the literature (prematurity, low birth weight [<2500 g], antenatal colonization, multiple-gestation pregnancy, maternal age <20 years, male infant sex, intrapartum fever, prolonged rupture of membranes) and meta-analyses to determine pooled estimates of risk. Results We included 27 articles, reporting 5315 cases. Prematurity (odds ratio [OR] 5.66; 95% confidence interval [CI]: 4.43–7.22), low birth weight (OR 6.73; 95% CI: 4.68–9.67), maternal colonization (2.67; [2.07–3.45]), and multiple-gestation pregnancies (OR 8.01; 95% CI: 5.19–12.38) were associated with an increased risk of LOGBS. Conclusions Prematurity/low birth weight and maternal colonization are major risk factors for LOGBS. Future GBS vaccine studies should try to establish the optimal time for vaccination during pregnancy to protect preterm infants. [ABSTRACT FROM AUTHOR]

Aim: Breast and cervical cancers have emerged as major global health challenges and disproportionately affect women in low- and middle-income countries, including Nepal. This scoping review aimed to map the knowledge, attitudes and screening practices for these cancers among Nepali women to improve cancer outcomes and reduce inequality. Methods: Five electronic databases (CINAHL, Embase, Global Health, PsycINFO and PubMed), grey literature, and reference and citation lists were searched for articles published in English up to June 2021. Articles were screened against inclusion/exclusion criteria, and data from eligible studies were extracted. Results were summarised narratively. Results: The search yielded 615 articles, 38 of which were included in this scoping review (27 cervical cancer, 10 breast cancer, 1 both cancers). Levels of knowledge regarding breast and cervical varied widely. The main knowledge gaps were misconceptions about symptoms and risk factors, and poor understanding of screening behaviours. Screening practices were mostly inadequate due to socio-cultural, geographical or financial barriers. Positive attitudes towards cervical screening were associated with higher education and increased knowledge of screening modalities. Higher levels of knowledge, (health) literacy and participation in awareness campaigns facilitated breast cancer screening. Conclusion: Knowledge and screening practices for breast and cervical cancer among Nepali women were poor and highlight the need for awareness and education programmes. Future research should explore community health worker-led awareness and screening interventions for cervical cancer, and programmes to increase the practice of breast self-examination and clinical breast examinations to support early diagnosis of breast cancer. [ABSTRACT FROM AUTHOR]

Streptococcus agalactiae (group B streptococcus; GBS) is an important human pathogen causing pneumonia, sepsis and meningitis in neonates, as well as infections in pregnant women, immunocompromised individuals, and the elderly. For the future control of GBS-inflicted disease, GBS surface exposed proteins are particularly relevant as they may act as antigens for vaccine development and/or as serosubtype markers in epidemiological settings. Even so, the genes encoding some of the surface proteins established as serosubtype markers by antibody-based methods, like the R3 surface protein, are still unknown. Here, by examining a Norwegian GBS collection consisting of 140 strains, we find that R3 protein expression correlates with the presence of the gene sar5. By inducible expression of sar5 in an R3-negative bacterial strain we show that the sar5 gene product is specifically recognized by an R3 monoclonal antibody. With this we identify sar5 as the gene encoding the R3 surface protein, a serosubtype marker of hitherto unknown genetic origin. [ABSTRACT FROM AUTHOR]

Introduction: Thymine auxotrophic in vitro mutants of Escherichia coli were first reported in the mid-20th century. Later, thymine-dependent clinical strains of E. coli as well as other Enterobacterales, Enterococcus faecalis and Staphylococcus aureus have been recognized as the cause of persistent and recurrent infections. Objectives: The aim of this study was to characterize the phenotype and investigate the molecular basis of thymine auxotrophy in ten E. coli isolates obtained at different time points from a patient with recurrent bloodstream infection (BSI) due to a chronic aortic graft infection treated with Trimethoprim/sulfamethoxazole (TMP-SMX). Methods: Clinical data was obtained from hospital records. Growth characterization and antimicrobial susceptibility testing to TMP-SMX was performed on M9 agar and in MH broth with different thymine concentrations (0.5, 2, 5, 10 and 20 μg/mL), on Mueller-Hinton (MH) and blood agar. Whole genome sequencing (WGS) was performed on all E. coli isolates. Results: E. coli were isolated from ten consecutive BSI episodes from a patient with chronic aortic graft infection. Six of these isolates were resistant to TMP-SMX when assayed on blood agar. Growth experiments with added thymine confirmed that these isolates were thymine-dependent (thy-), and revealed growth defects (slower growth rate and smaller colony size) in these isolates relative to thy+ isolates (n = 4). WGS indicated that all isolates were of the same clonal lineage of sequence type 7358. Genomic analysis revealed a G172C substitution in thyA in all TMP-SMX resistant isolates, while mutations affecting genes involved in the deoxyribose salvage pathway (deoB and deoC) were identified in eight isolates. Conclusion: This case highlights the risk of resistance development to TMP-SMX, especially for long-term treatment, and the possible pitfalls in detection of growth-deficient subpopulations from chronic infections, which could lead to treatment failure. [ABSTRACT FROM AUTHOR]

Background: Mastitis is one of the most expensive diseases in the dairy industry. It causes heavy monetary losses by decreasing milk production and treatment cost. Streptococcus agalactiae, the cause of contagious bovine mastitis, possesses various virulence factors that contribute to pathogenicity. Aims: The main aim of the study was to evaluate the distribution of virulence genes of S. agalactiae. Methods: In the current work, 98 Streptococcus species were isolated from 320 milk samples, collected from Veterinary Clinical Complex, Junagadh. Out of the isolates, 42 S. agalactiae isolates were used for virulence genes detection. Results: All Streptococcus spp. were confirmed at genus level by targeting tuf gene, and S. agalactiae was identified at species level by targeting 16S rRNA gene. For virulence gene detection, scpB, cfb, and cylE genes were targeted. Of 42 S. agalactiae isolates, 15, 16, and 10 isolates possessed scpB, cfb, and cylE genes, respectively. Conclusion: This study aids us to know virulence characteristics and mechanisms responsible for the development of new strains in mastitis epidemiology in response to prevention and control strategies. [ABSTRACT FROM AUTHOR]

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Background The incidence of tularemia has recently increased throughout Europe. Pediatric tularemia typically presents with ulceroglandular or glandular disease and requires antimicrobial therapy not used in the empirical management of childhood acute lymphadenitis. We describe the clinical presentation and course in a case series comprising 20 patients. Methods This is a retrospective analysis of a single-center case series of microbiologically confirmed tularemia in patients <16 years of age diagnosed between 2010 and 2021. Results Nineteen patients (95%) presented with ulceroglandular (n = 14) or glandular disease (n = 5), respectively. A characteristic entry site lesion (eschar) was present in 14 (74%). Fever was present at illness onset in 15 patients (75%) and disappeared in all patients before targeted therapy was initiated. The diagnosis was confirmed by serology in 18 patients (90%). While immunochromatography was positive as early as on day 7, a microagglutination test titer 1:≥160 was found no earlier than on day 13. Sixteen patients (80%) were initially treated with an antimicrobial agent ineffective against F. tularensis. The median delay (range) from illness onset to initiation of targeted therapy was 12 (6–40) days. Surgical incision and drainage were ultimately performed in 12 patients (60%). Conclusions Pediatric tularemia in Switzerland usually presents with early, self-limiting fever and a characteristic entry site lesion with regional lymphadenopathy draining the scalp or legs. Particularly in association with a tick exposure history, this presentation may allow early first-line therapy with an agent specifically targeting F. tularensis , potentially obviating the need for surgical therapy. [ABSTRACT FROM AUTHOR]