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Volume 74,
Issue 3,
2025
Volume 74, Issue 3, 2025
- Editorials
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- Letters
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- Reviews
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Cases of high consequence infectious diseases identified in the UK, 1962–2023
More LessThe management of patients with acute infectious diseases can present significant challenges, especially if the causative agent has a propensity for person-to-person transmission. In such cases, effective patient management is dependent on both rapid identification of disease and the provision of necessary medical care while adhering to suitable infection prevention and control measures to reduce the potential for onwards transmission. The UK has operated a defined system for managing patients with high consequence infectious diseases (HCIDs) since the 1970s, when protocols were first implemented following the first descriptions of several viral haemorrhagic fever diseases, including Marburg virus disease, Lassa fever and Ebola virus disease (EVD). While more than 200 people with HCIDs have been treated in UK hospitals since the 1970s, most of these patients had COVID-19 or mpox during the early phases of new public health emergencies of international concern (PHEICs), prior to their removal from the UK HCID list in March 2020 and June 2022, respectively. Excluding PHEICs, 26 patients have been treated in HCID treatment centres between 1962 and 2023: 10 patients with Lassa fever, 7 with mpox prior to the 2022 PHEIC, 4 with Middle East respiratory syndrome (MERS), 4 with EVD and 1 with Crimean-Congo haemorrhagic fever (CCHF). In total, 15 additional HCID patients were identified where treatment in a specialist centre did not occur due to retrospective diagnosis (4 patients with Lassa fever), mild or moderate illness [5 patients with avian influenza A(H5N1), 1 with MERS and 1 with CCHF] or death prior to transfer (2 patients with Lassa fever, 1 with CCHF and 1 with pneumonic plague). Here we summarize the UK HCID experience, including details about their detection, patient management and outcomes.
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- Perspectives
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Sepsis in silico: definition, development and application of an electronic phenotype for sepsis
More LessRepurposing electronic health record (EHR) or electronic medical record (EMR) data holds significant promise for evidence-based epidemic intelligence and research. Key challenges include sepsis recognition by physicians and issues with EHR and EMR data. Recent advances in data-driven techniques, alongside initiatives like the Surviving Sepsis Campaign and the Severe Sepsis and Septic Shock Management Bundle (SEP-1), have improved sepsis definition, early detection, subtype characterization, prognostication and personalized treatment. This includes identifying potential biomarkers or digital signatures to enhance diagnosis, guide therapy and optimize clinical management. Machine learning applications play a crucial role in identifying biomarkers and digital signatures associated with sepsis and its sub-phenotypes. Additionally, electronic phenotyping, leveraging EHR and EMR data, has emerged as a valuable tool for evidence-based sepsis identification and management. This review examines methods for identifying sepsis cohorts, focusing on two main approaches: utilizing health administrative data with standardized diagnostic coding via the International Classification of Diseases and integrating clinical data. This overview provides a comprehensive analysis of current cohort identification and electronic phenotyping strategies for sepsis, highlighting their potential applications and challenges. The accuracy of an electronic phenotype or signature is pivotal for precision medicine, enabling a shift from subjective clinical descriptions to data-driven insights.
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- Clinical Profile
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Parachlamydia acanthamoebae: disease-causing pathogen or opportunistic bystander?
Introduction. Parachlamydia acanthamoebae is an obligate intracellular bacterium related to disease-causing bacteria like Chlamydia trachomatis and Chlamydia pneumoniae and is thus classified within the Chlamydiales order. Parachlamydia was initially discovered within an Acanthamoeba strain isolated from water in a humidifier during an investigation of an outbreak of respiratory infections in humans.
Gap Statement. The disease-causing potential of this bacterium is not fully understood, but Parachlamydia has been associated with bronchiolitis, bronchitis, aspiration pneumonia and community-acquired pneumonia in humans. Additionally, diagnostic testing for Parachlamydia infection is not routinely performed, indicating that prevalence is underreported.
Aim. This JMM profile aims to gauge what is currently known about the pathogenic potential of P. acanthamoebae and bring awareness to gaps in knowledge.
Results. Amoebae appear to be the main reservoir of P. acanthamoebae and likely enter the nasal passages through contaminated water sources or contact with contaminated animals. The infected amoebae may then descend to the lower respiratory tract where the lytic cycle is triggered, causing human infection.
Conclusion. By implementing serology and molecular testing, as well as conducting additional epidemiological studies, a better understanding of the association of human colonization with disease outcomes can be achieved.
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- Antimicrobial Resistance
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Epidemiology and management of infections in critically ill neonates: findings from a cohort study in a Brazilian neonatal intensive care unit
Introduction. Healthcare-associated infections (HAIs) are the leading cause of preventable death in neonatal intensive care units (NICUs), particularly among very low birth weight (VLBW) infants.
Hypothesis/Gap Statement: VLBW neonates are at higher risk of HAIs, particularly those caused by Gram-negative bacteria (GNB) and fungi, which can negatively impact their survival and prolong hospitalization.
Aim. To determine the risk factors, aetiology, antimicrobial susceptibility and clinical outcomes of HAIs in VLBW neonates in a Brazilian NICU.
Methodology. This retrospective cohort study analysed the medical records of VLBW newborns admitted to the NICU from January 2015 to December 2022.
Results. Among VLBW neonates, 269/670 (40.1%) developed HAIs and 203/670 (30.3%) developed sepsis. The incidence of HAIs (54.5% vs. 36.2%) and sepsis (49.7% vs. 25%) was higher in neonates weighing less than 750 g. The median birth weight of infected newborns was 960 g, and the median age of infection onset was 16 days. There were 292/456 (64%) infections caused by Gram-positive bacteria, 138/456 (30.3%) by GNB and 26/456 (5.7%) by fungi. Of the isolates, 277/456 (60.7%) were multidrug-resistant. Newborns weighing less than 750 g or infected with GNB and/or fungi had lower survival rates. Previous use of antifungals was the main predictor of infection (P<0.01; odds ratio=4.21). Infections prolonged hospital stay from 25 to 42 days. The mortality rate was 17.6%, with a case lethality rate of 16.4%; 75% of deaths in the infected group were due to sepsis.
Conclusion. The high incidence of infection emphasizes the need for infection control and antimicrobial management. Low birth weight is associated with increased risk of infection and decreased survival. The increase in GNB and fungal infections requires prevention and treatment strategies to reduce neonatal morbidity and mortality.
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Multidrug resistance in group B Streptococcus causing urinary tract infection exposes an erythromycin-driven protective effect against oxidative stress
Multidrug resistance has been reported in group B Streptococcus (GBS) from various origins, but rates among urinary tract infection (UTI) isolates are largely unknown. Erythromycin, a second-line antibiotic for GBS for which high rates of resistance have been reported, was recently shown to support the resistance of Staphylococcus to oxidative stress. To survey multidrug-resistant (MDR) GBS from UTI and to investigate the effect of erythromycin exposure on the bacteria’s ability to resist oxidative stress, we determined the antibacterial activity of 18 antibiotics against 292 GBS UTI isolates by disc diffusion and used in vitro growth assays of MDR GBS exposed to erythromycin to examine relative resistance to oxidative stress in the form of H2O2. A high proportion of all 292 GBS isolates (33.6%) were MDR, reflecting high rates of resistance to four antibiotics: azithromycin (44.5%), clindamycin (26%), erythromycin (36.3%) and tetracycline (81.5%); however, no resistance was detected for any other antibiotics tested. Rates of resistance were not significantly different when analysed according to clinical origins (acute and recurrent UTI, asymptomatic bacteriuria). The growth of MDR GBS was attenuated and severely inhibited by exposure to erythromycin and H2O2, respectively. Surprisingly, exposure of MDR GBS to erythromycin significantly relieved the severe growth inhibitory effect of H2O2, signifying a partial rescue effect of the antibiotic. The GBS isolates in this study exhibit high levels of multidrug resistance without an association between resistance and clinical origin. Exposure of MDR GBS to erythromycin can partially counteract the severe growth inhibitory effect from H2O2.
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Fractional inhibitory concentration of bio-actives from agricultural waste disassembles biofilms and quenches virulence of nosocomial pathogens
More LessIntroduction. The contact surfaces in hospitals serve as reservoirs for pathogens and account for 20–40% of hospital-acquired infections. This resistance is mainly attributed to the biofilm-forming ability of the microbes. These biofilms restrict the entry of the antibiotics to penetrate them, thus giving rise to drug resistance. Hence, there is a renewed interest in formulating an environmentally friendly, non-allergic, quick mode of action, broad-spectrum disinfectant.
Hypothesis. We hypothesize that the pure compounds present in the pyrolysis aqueous phase could act as an anti-infective and anti-biofilm agent.
Aim. The present work investigates the effectiveness of furfuryl alcohol, 2-methyl-2-cyclopentenone and guaiacol as effective anti-infective agent followed by testing its biofilm eradication potential against the mixed species of multidrug-resistant pathogens such as Acinetobacter baumannii, methicillin-resistant Staphylococcus aureus and Candida auris.
Methodology. The MIC and fractional inhibitory concentrations (FIC) of the pure compounds were determined using checkerboard assay for two-compound and three-compound combinations. The biofilm eradication concentration was performed on stainless coupons, followed by RNA isolation and quantitative PCR (qPCR) analysis to elucidate virulence gene downregulation.
Results. The individual MICs of furfuryl alcohol, 2-methyl-2-cyclopentenone and guaiacol were found to be 8%, 9% and 2% (v/v), respectively. The two-compound combination FIC index of 0.75 showed partial synergy between the compounds, while the three-compound combination showed an additive effect with a FIC index of 0.87. Further, at ½ FIC (biofilm inhibitory concentration), the compounds showed 52% eradication of preformed biofilms on the hospital contact surfaces (stainless steel). The growth and time-to-kill curve showed that the compounds were not lethal to planktonic cells at BIC. Finally, the qPCR analysis showed a reduction in the expression levels of biofilm and adhesion genes, while the Quorum sensing (QS) genes were affected much more, elucidating a possible eradication mechanism.
Conclusion. From this study, we have found a new class of compounds that have potential disinfecting ability. With the current knowledge, the future lead would be to effectively use them in disinfectant formulations.
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Evaluation of whole-genome sequencing protocols for detection of antimicrobial resistance, virulence factors and mobile genetic elements in antimicrobial-resistant bacteria
Introduction. Antimicrobial resistance (AMR) poses a critical threat to global health, underscoring the need for rapid and accurate diagnostic tools. Methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae (ESBL-Kp) are listed among the World Health Organization’s priority pathogens.
Hypothesis. A rapid nanopore-based protocol can accurately and efficiently detect AMR genes, virulence factors (VFs) and mobile genetic elements (MGEs) in MRSA and ESBL-Kp, offering performance comparable to or superior to traditional sequencing methods.
Aim. Evaluate whole-genome sequencing (WGS) protocols for detecting AMR genes, VFs and MGEs in MRSA and ESBL-Kp, to identify the most accurate and efficient tool for pathogen profiling.
Methodology. Five distinct WGS protocols, including a rapid nanopore-based protocol (ONT20h) and four slower sequencing methods, were evaluated for their effectiveness in detecting genetic markers. The protocols' performances were compared across AMR genes, VFs and MGEs. Additionally, phenotypic antimicrobial susceptibility testing was performed to assess concordance with the genomic findings.
Results. Compared to four slower sequencing protocols, the rapid nanopore-based protocol (ONT20h) demonstrated comparable or superior performance in AMR gene detection and equivalent VF identification. Although MGE detection varied among protocols, ONT20h showed a high level of agreement with phenotypic antimicrobial susceptibility testing.
Conclusion. The findings highlight the potential of rapid WGS as a valuable tool for clinical microbiology, enabling timely implementation of infection control measures and informed therapeutic decisions. However, further studies are required to optimize the clinical application of this technology, considering costs, availability of bioinformatics tools and quality of reference databases.
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- Clinical Microbiology
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Evaluation of the safety and effectiveness of combination therapy with 1% ivermectin solution in moderate to severe rosacea: a cohort study
Introduction. Rosacea is a common chronic dermatological disease that negatively affects the quality of life of patients.
Hypothesis. Combination therapy with 1% ivermectin solution alongside systemic treatment methods is more effective in reducing the severity of moderate to severe papulopustular rosacea symptoms compared with traditional treatment methods alone.
Aim. This study is aimed at finding new approaches to the treatment of moderate and severe forms of rosacea.
Methodology. This research compared the main group receiving ivermectin with a control group getting conventional treatment to assess the safety and efficacy of 1% ivermectin combination therapy in 70 individuals with moderate to severe rosacea. At weeks 2, 4 and 8, the dynamics of clinical symptoms were evaluated using a 4-point scale.
Results. The use of combination therapy with ivermectin led to a more pronounced improvement in the clinical picture. Already at week 4, a 48–54% decrease in symptoms was recorded in the main group, while in the control group, it was only by 25–30%. By week 8, an almost complete reduction of the main manifestations was observed in the main group (78–88% decrease). Regression analysis confirmed that combination therapy with ivermectin was a key factor determining a more substantial clinical improvement, regardless of age, gender and the initial severity of the patient’s condition. In addition, a much more pronounced decrease in the number of Demodex ticks was recorded in the main group. The effectiveness of combination therapy with ivermectin did not depend on the demographic or clinical characteristics of patients, which makes it a universal method of treating rosacea. No serious side effects have been reported in any patient receiving combination therapy, which indicates its safety.
Conclusion. This approach can be a valuable addition to existing strategies for the treatment of this chronic dermatological disease.
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Impact of cyclosporine A on the progression of ocular surface diseases: treatment efficacy and potential complications
Introduction. Eye diseases are widespread all over the world and, if left untreated, can lead to blindness.
Hypothesis. The use of 0.05% cyclosporine A (CsA) solution for the treatment of dry eye causes a decrease in discomfort and pain and improves objective measures such as tear film breakdown time, Schirmer test results and Oxford scale scores due to its anti-inflammatory and immunomodulatory properties that contribute to improved tear film stability and tear production.
Aim. This study aimed to investigate the impact of CsA on the progression of ocular surface diseases.
Methodology. An experiment was conducted on the basis of the FOCUS ophthalmology centre, Kazakhstan. A group of 100 individuals diagnosed with mild to severe dry eye illness were administered 0.05% CsA eye drops as part of the treatment protocol.
Results. The positive effect is explained by the anti-inflammatory and immunomodulatory effects of CsA. The study showed that the use of 0.05% CsA solution for the treatment of ocular surface disease led to a decrease in discomfort and pain, as well as an improvement in objective measures, including tear film breakdown time, Schirmer test results and Oxford scale scores. The visual analogue scale showed a significant reduction in symptoms, from 6.8 points at baseline to 3.7 points at day 60. In total, 20% of patients reported moderate side effects, such as pain during instillation and redness of the eye surface.
Conclusion. It is concluded that the use of these drops reduced pain, improved patient condition and enhanced indicators such as the visual analogue scale, tear film breakup time, Schirmer test and Oxford scale of corneal and conjunctival staining. This study differs from the previous ones in that it focuses on the efficacy of 0.05% CsA solution in the treatment of dry eye and also examines the spectrum and frequency of side effects, which is not sufficiently covered in previous studies.
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Geographical and temporal variations of serogroups and clonal types of Neisseria meningitidis involved in culture-confirmed invasive meningococcal disease in Canada, 2015–2023
Introduction. Invasive meningococcal disease (IMD) is a nationally notifiable illness in Canada due to its potential severity and transmissibility. Vaccination strategies differ by province/territory and are informed by changes in the antigenic characteristics of circulating strains.
Gap Statement. Though IMD statistics are tracked at a provincial/territorial level, there is a lack of published data characterizing trends in the epidemiology of this disease at a national level.
Aim. To examine the epidemiology of culture-confirmed IMD in Canada during the period of 2015–2023.
Methodology. Meningococcal isolates sent to the National Microbiology Laboratory Branch between 2015 and 2023 as part of routine national surveillance were characterized for serogroup by bacterial agglutination and genetic methods. Clonal analysis was done by MLST. Demographic information was derived from requisition forms accompanying the samples.
Results. The proportion of IMD caused by serogroup W meningococci (MenW) in 2015–2023 was 30.0% with more (62.9%) MenW cases detected in western provinces. Serogroup B meningococci (MenB) IMD was more common (53.4%) in Quebec and Atlantic Canada. Clonal analysis reveals 168 distinct sequence types between 2015 and 2023, with 103 belonging to MenB. The average age of MenB cases during this time was 29.1 years, significantly younger than serogroup C (MenC) (45.3 years), serogroup Y (MenY) (48.3 years) and MenW (43.0 years) patients. Additionally, 31.5% of MenB and 21.7% of MenC IMD isolates were collected from cerebrospinal fluid (CSF) or brain samples, which were significantly higher than that for MenY (12.2%) and MenW (7.3%) isolates.
Conclusions. Results from this and previous studies showed temporal and geographical variations in the serogroups causing IMD in Canada. MenB also showed the most genetic diversity, caused IMD in a significantly younger population and was more often isolated from CSF and brain samples than other serogroups.
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- Disease, Diagnosis and Diagnostics
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Surveillance of Salmonella and antimicrobial resistance in industrial poultry enterprises: biofilm-forming strains and critical control points
Introduction. Salmonella contamination in the poultry industry poses substantial health risks, especially due to biofilm-forming strains that resist disinfection and antibiotic treatment. Biofilm-forming Salmonella strains are particularly challenging to control, as they adhere to surfaces in production environments, leading to persistent contamination. This study assesses the prevalence of Salmonella, examines antibiotic resistance patterns and evaluates biosecurity effectiveness at poultry farms in Kazakhstan.
Hypothesis/Gap Statement. There is limited data on the prevalence and antibiotic resistance of biofilm-forming Salmonella strains in Kazakhstan’s poultry industry, highlighting a need to characterize these strains to inform effective control measures.
Aim. The purpose of this study was to systematically identify and characterize Salmonella strains, including biofilm-forming types, within industrial poultry enterprises in Kazakhstan.
Methodology. A total of 660 samples were collected from various poultry production sites, including feed, water sources, cloacal flushes and shoe covers. Salmonella detection followed standardized protocols, and antibiotic sensitivity of identified strains was analysed to evaluate resistance patterns.
Results. Salmonella was detected in 11.5% (95% CI) of the 660 samples, with the highest contamination observed in shoe covers, cloacal flushes, feed and water. This prevalence rate indicates a significant presence of the pathogen in the country’s poultry production chain, falling between the higher rates seen in countries like China (22.2%) and Egypt (29.1%) and the lower rates observed in countries like Brazil (3.4%). The most prevalent strain was Salmonella gallinarum-pullorum (61.8%), followed by Salmonella typhimurium (18.4%) and Salmonella enteritidis (14.5%). Antibiotic sensitivity analysis revealed that S. gallinarum-pullorum was largely susceptible to common antibiotics, while S. typhimurium displayed considerable resistance, emphasizing the need for alternative treatments.
Conclusion. The findings underscore the importance of strict sanitary and hygiene standards throughout poultry production, with a particular focus on managing biofilm-forming Salmonella strains. Implementing comprehensive Hazard Analysis and Critical Control Points protocols is essential to address contamination hotspots effectively. Future studies should investigate genetic mechanisms underlying biofilm formation and resistance in Salmonella strains to inform targeted interventions, ultimately improving food safety and public health outcomes.
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- Medical Mycology
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Antimicrobial and antiparasitic potential of lupeol: antifungal effect on the Candida parapsilosis species complex and nematicidal activity against Caenorhabditis elegans
Marrie da Silva Dutra, Paulo Ricardo Monteiro Araújo, Maria Gleiciane da Rocha, Vinícius Carvalho Pereira, Alyne Soares Freitas, Raissa Geovanna Pereira Lopes, Pedro Filho Noronha Souza, Raquel Carvalho Montenegro, Waldemiro de Aquino Pereira-Neto, Géssica dos Santos Araújo, Rossana de Aguiar Cordeiro, José Júlio Costa Sidrim, Glaucia Morgana de Melo Guedes, Débora de Souza Collares Maia Castelo-Branco and Marcos Fábio Gadelha RochaIntroduction. There is growing concern about infections caused by non-albicans Candida species, including species of the Candida parapsilosis complex – which have seen a considerable increase in cases during the COVID-19 pandemic – in addition to concern about nematode resistance to currently used anthelmintics.
Gap Statement. Lupeol is a triterpenoid phytosterol that has a wide range of biological activities, although its antifungal and antiparasitic potential is still poorly explored. Additionally, its effect on the biofilm of the C. parapsilosis species complex has not yet been studied.
Aim. This study aimed to investigate the antifungal effect of lupeol against C. parapsilosis complex species, in planktonic cells and mature biofilms, as well as its nematicidal potential against Caenorhabditis elegans. In addition, molecular docking was performed to identify potential target molecules for lupeol’s antifungal effect.
Methodology. Twelve strains of C. parapsilosis species complex were used. Planktonic susceptibility was performed through the broth microdilution assay, while the antibiofilm effect was investigated by measuring the biomass and metabolic activity. The antifungal mechanism of action of lupeol was investigated by target fishing. The evaluation of the nematicidal effect was performed using the C. elegans infection model.
Results. Lupeol demonstrated antifungal activity against planktonic cells with a MIC between 64 and 512 µg ml−1. In mature biofilms, lupeol was able to reduce biomass starting from a concentration of 1024 µg ml−1 and reduce metabolic activity from a concentration of 64 µg ml−1. It was observed that there was interaction of lupeol with the enzyme 14α-demethylase. Furthermore, lupeol had a nematicidal effect from a concentration of 64 µg ml−1.
Conclusion. Lupeol exhibits an antifungal effect on the C. parapsilosis species complex, in the planktonic and mature biofilm forms, possibly by affecting the ergosterol synthesis. Lupeol further demonstrated a nematicidal potential.
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- Microbiome and Microbial Ecology in Health
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Comprehensive toolkit integrating lifestyle and clinical questionnaires with gut microbiota profiling via rectal swabs: application in intensive care cirrhotic patients
Introduction. The study of gut microbiota is now an essential dimension in many clinical studies. For instance, microbiota diversity investigation can help us to better manage cirrhotic patients by the identification of markers of severity and the identification of possible sources of pathogens.
Hypothesis/Gap Statement. Conducting clinical research on gut microbiota for fragile patients in intensive care units, such as cirrhotic patients, poses significant challenges.
Aim. In this study, we developed a comprehensive toolkit for investigating gut microbiota in fragile patients using rectal swabbing combined with straightforward lifestyle and clinical questionnaires.
Methodology . We applied this prospective approach to 49 well-phenotyped cirrhotic patients as a function of their compensation status (compensated patients with outpatients’ recruitment vs decompensated patients in intensive care units).
Results . Our results, consistent with the literature, showed that liver function impairment is associated with lower microbiota diversity. Additionally, we monitored aerobic microbiota in decompensated cirrhotic patients, observing the invasion of extended spectrum beta-lactamase (ESBL)-producing Escherichia coli in the gut’s aerobic microbiota prior to severe infection caused by these pathogens.
Conclusion. We propose this pragmatic methodology for larger cohort studies, aiming to enhance the monitoring of immunocompromised patients by using microbiota analysis as a predictive tool for the severity of associated pathologies and the identification of agents responsible for severe infections.
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Influence of menstrual cycle and oral contraception on taxonomic composition and gas production in the gut microbiome
Introduction. Oral contraceptives (OCs) are widely used for birth control and offer benefits such as menstrual cycle regulation and reduced menstrual pain. However, they have also been associated with an increased risk of cancer and reduced bone mass density.
Gap Statement. While the gut microbiome is known to interact with endocrine factors, the impact of hormonal OCs on its composition and function remains underexplored. Additionally, we explore the relationship of OC use and the microbiome to gas production, which can cause symptoms and be indicative of poor health.
Aim. This study investigates the effects of OCs on the diversity and composition of the gut microbiome and its association with breath hydrogen (H2) and methane (CH4) levels.
Methodology. We utilized 16S rRNA gene sequencing to analyse faecal samples from 65 women, comparing OC users with non-users at two menstrual cycle time points. Breath tests measured hydrogen and CH4 production. Data were analysed for microbial diversity, community composition and correlation with gas production.
Results. There were no differences in overall microbial diversity between OC users and non-users in samples collected on day 2 of the menstrual cycle. However, on day 21, we found a significant difference in microbial richness, suggesting a cycle-dependent effect of OCs on gut microbiota species richness but not composition. We found a strong correlation between H2 and CH4 concentrations and an interaction between OC use and the menstrual cycle on H2 and CH4 production. We also identified several taxa associated with both high levels of H2 and CH4 production and OC use.
Conclusion. Our study highlights the intricate relationships among hormonal contraceptives, the gut microbiota and gas production and connects shifts in the microbiome composition to gastrointestinal symptoms (e.g. gas production) that can impact overall health. This underscores the need for further research on the long-term effects of OCs and for the development of precise therapeutic strategies to address potential adverse effects. Our findings offer new perspectives on the microbiome–hormone–gas production nexus, potentially broadening our understanding of the systemic implications of OCs.
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- Molecular and Microbial Epidemiology
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Phenotype and genotype of carbapenem-resistant hypervirulent Klebsiella pneumoniae in a teaching hospital in Shanghai, China
More LessIntroduction. Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) is an emerging pathogen associated with severe clinical outcomes, prompting an urgent investigation into its genomic characteristics and pathogenic potential.
Hypothesis/Gap Statement. We hypothesize that CR-hvKP strains exhibit high-level resistance and high virulence, leading to their rapid spread in clinical settings and posing a serious threat to clinical treatment.
Aim. The aim of the study was to investigate the phenotype and genotype of CR-hvKP strains, reveal their resistance- and virulence-related genomic characteristics and elucidate the biological characteristics of high-virulence and high-resistance strains to provide molecular epidemiological data for clinical use.
Methodology. Carbapenem-resistant K. pneumoniae (CRKP) strains were obtained from clinical samples, from January 2013 to December 2018. PCR amplification was conducted to screen for carbapenem genes. To evaluate the virulence potential of the isolates, we conducted various tests, including a string test, Galleria mellonella larvae infection test, capsular polysaccharide synthesis genotyping and genetic sequencing analyses. We used PFGE, multilocus sequence typing and next-generation sequencing to detect the genetic relationship and homology of the strains.
Results. In this study, we obtained 500 strains of CRKP, among which 18 strains were identified as CR-hvKP. All CR-hvKP strains were multidrug-resistant, exhibiting high-level resistance to most β-lactam antibiotics, including carbapenems. All CR-hvKP strains except N5 were positive for blaKPC-2, of which 14 isolates belonged to capsular serotype K64. Ten unrelated PFGE types were identified by PFGE analysis. Based on the results of PFGE, a total of 12 CR-hvKP isolates were selected from the 18 isolates for further testing, and 9 isolates had high homology with pLVPK virulence-related plasmids. All CR-hvKP strains showed high virulence in the Galleria mellonella infection model.
Conclusions. The study revealed the resistance- and virulence-related genomic characteristics of CR-hvKP strains and confirmed the high virulence of these strains. These results are of great significance for understanding the epidemiological characteristics and clinical treatment of CR-hvKP and provide basic data for the formulation of corresponding prevention and control strategies.
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Genotypic diversity of the Helicobacter pylori vacA c region and its correlation with gastric disease outcomes
Introduction . Helicobacter pylori infection is a major cause of peptic ulcer and gastric adenocarcinoma. The infection progression to severe diseases depends on several factors, including bacterial ones. CagA and VacA are two major virulence factors widely studied and implicated in H. pylori diseases.
Gap statement. Although the allelic prevalence of the s, m, i and d regions of the H. pylori vacA gene and their relation with gastric disease outcomes have been largely studied, there is a gap in knowledge regarding the prevalence and the association of the vacA c region with those pathologies. This polymorphic region could exhibit a large variability which might impact the virulence of the bacterium and the severity of gastric damage.
Aim. The aim of this study was to investigate the prevalence of H. pylori vacA c alleles and to assess the association of vacA mosaicism with gastric damage in a large Moroccan population.
Methodology. H. pylori positive gastric biopsies, obtained in 709 consenting patients who consulted the gastroenterology department of the Hassan II University Hospital of Fez (Morocco) for clinical endoscopy, between 2009 and 2019, were used in this study. DNA extracted from the biopsy samples was used to determine the vacA c genotype using specific PCRs. H. pylori cagA, vacA s, vacA m, vacA d and vacA i genotypes of these samples were previously determined.
Results. The vacA c2 genotype was detected in 44.7% of samples and the vacA c1 genotype in 16.5% of cases. Multiple infections (detection of the two vacA c allelic forms) were obtained in 9% of samples. Correlation of H. pylori vacA c genotype with pathologies showed that the vacA c1 allele was strongly associated with the risk of gastric cancer (GC) [odds ratio=3.14, confidence intervals 95% (1.08–9.09)].
Conclusion. The results of this study confirm that despite the large H. pylori genetic diversity, the genotypic distribution is marked by a predominance of the less virulent strains in Morocco. Also, even if vacA allelic combinations seem to impact the toxicity of this bacterium, patients infected with H. pylori vacA c1 genotype are more likely to develop GC than those infected by H. pylori vacA c2 genotype.
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Predomination of hypervirulent ST283 and genetic diversity of levofloxacin resistance in multidrug-resistant, hypervirulent Streptococcus agalactiae in Thailand
Introduction. Group B Streptococcus (GBS) is a multi-host pathogen causing pneumonia and meningitis in humans as well as streptococcal diseases in tilapia and mastitis in cattle. Thailand has experienced a significant increase in GBS infections that greatly impact health and economics.
Gap statement. The antimicrobial resistance (AMR) and genotype data of GBS in Thailand are still limited and require further study.
Aim. This study aimed to describe AMR profiles and molecular characteristics, especially antimicrobial resistance genes (ARGs) and virulence factor (VF) genes of GBS in Thailand.
Methodology. AMR profiles of 221 GBS isolates from humans, fish and freshwater were examined. Whole-genome sequencing of 41 representative isolates was used to investigate capsular genotypes and sequence types (STs), ARGs and VF genotypes.
Results. All GBS isolates were susceptible to penicillin; the majority (99.1%) showed resistance to tetracycline. In addition, the rates of resistance to clindamycin, erythromycin and levofloxacin were 22.6%, 20.4% and 2.3%, respectively; multidrug-resistant (MDR) isolates (TE-E-CM and TE-E-CM-LVX) were 19.5%. Among 41 representative isolates, the dominant types were capsular genotype III (63.4%) and ST283 (43.9%). ARGs associated with resistance to tetracycline (tetM, tetO and tetS), erythromycin (ermB, ermA, mefA and msrD) and clindamycin (lsaC, lsaE and lnuB) were identified. Additionally, point mutations responsible for levofloxacin resistance, S81L in GyrA, S79F/Y in ParC and H221Y in ParE, were found. The MDR isolates belonged to various STs, predominantly clustering in capsular types III (60.0%) and Ib (30.0%). The MDR-hypervirulent ST17 and ST19 harboured multiple ARGs and mutations affecting quinolone resistance. Different VF gene patterns were found among hypervirulent STs (ST12, ST17, ST19 and ST283). Notably, a unique nt deletion [c.(1013_1020)delG] in pilA was found only in ST283.
Conclusion. This study elucidated significant antimicrobial characteristics of a substantial number of GBS in Thailand. Moreover, the distribution of the hypervirulent ST283 and the genotypes of MDR-hypervirulent GBS were first described.
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Intratype variants and high genotypic diversity of human papillomavirus with polymorphisms in the antigenic hypervariable loops of the L1 protein from women living with human immunodeficiency virus in Northeastern Brazil
Introduction. The human papillomavirus (HPV) is one of the main oncogenic viruses. High-risk HPV types are associated with the development of cervical cancers. In addition, it is known that some mutations in HPV genes, or variant viral lineages, have been associated with greater oncogenic risk.
Gap statement. The L1 protein is the major component of the viral capsid and is therefore used in currently available vaccines. However, the characterization of mutations in the L1 gene, which is relevant to increasing the knowledge of the immune escape mechanisms used by the virus, is still incipient.
Aim. This study aimed to characterize mutations associated with antigenic domains in the L1 protein of HPVs isolated from cervical samples of women living with HIV in Northeastern Brazil.
Methodology. L1 gene sequences were obtained from the samples, and the mutations and the viral variants were characterized. Phylogenetic and functional analyses of the structure of the L1 protein were carried out.
Results. A total of 41 HPV variant isolates were obtained, distributed among 16 different viral types. Of this, 25 non-synonymous mutations were evaluated regarding the stability of the L1 protein. It was observed that 10 of these mutations were predicted to increase, and 14 to decrease, the stability of the L1 protein and that most of them occurred in the FG hypervariable antigenic loop.
Conclusion. These results add useful knowledge to understanding the biological and immunological aspects of HPV variants and the impact of these mutations on the development of vaccine strategies.
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