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Article
Medicine and Pharmacology
Epidemiology and Infectious Diseases

Eleni Mylona

,

Sofia Kostourou

,

Dimitroula Giankoula

,

Chrysoula Kolokotroni

,

Paraskevas Tsilikis

,

Nikolaos Koudoumnakis

,

Maria Papagianni

,

Dimitris C. Kounatidis

,

Natalia G. Vallianou

,

Efstathia Perivolioti

+1 authors

Abstract: Background: Carbapenem-resistant Klebsiella pneumoniae (CRKp) remains a critical driver of antimicrobial resistance (AMR) in hospital settings worldwide. Methods: This study examined trends in CRKp bloodstream infections over a seven-year period (2019–2025) in a tertiary care hospital in Greece, with particular attention to resistance patterns and patient outcomes, including the impact of the COVID-19 pandemic. Results: A total of 671 non-duplicate CRKp isolates were analyzed and classified into three groups: KPC producers (67.4%), dual carbapenemase producers (17.4%), and single metallo-β-lactamase (MBL) producers (15.2%). Overall incidence showed a slight but non-significant increase over time. KPC-producing strains rose significantly until 2022 (p<0.001), followed by a marked decline (p<0.001). In contrast, dual carbapenemase producers—mainly KPC combined with VIM or NDM—and single-MBL producers, particularly NDM, increased steadily, indicating a notable epidemiological shift. Resistance to aminoglycosides and tigecycline increased around 2021, followed by partial declines, whereas colistin resistance demonstrated a continuous upward trend throughout the study period. Despite phenotypic differences, overall mortality remained high, with no statistically significant differences between groups (p = 0.37), likely reflecting either the severity of patients’ clinical condition or inadequate empirical antibiotic therapy. Conclusions: This study highlights a dynamic evolution in CRKp epidemiology with decreasing KPC dominance and increasing prevalence of MBL- and dual carbapenemase- producing strains. This transition, which became evident during and after the COVID-19 pandemic, underscores ongoing epidemiological adaptation and the urgent need for improved antimicrobial stewardship, rapid diagnostics, and broader access to effective therapies.

Article
Medicine and Pharmacology
Epidemiology and Infectious Diseases

Dimitris M. Manias

,

Dimitris G. Patsatzis

,

Haralampos Hatzikirou

,

Dimitris A. Goussis

Abstract: We present a robust, data-efficient framework for early outbreak assessment using multiscale analysis and Computational Singular Perturbation (CSP). This framework overcomes the shortcomings of the standard compartmental epidemiological models, which often struggle with parameter identifiability during the early stages of a pandemic, limiting considerably their predictive utility when data is sparse. Rather than relying on curve-fitting population profiles, which are sensitive to uncertainty, our approach isolates the dominant "explosive" time scale that characterizes the outbreak’s intensity and duration. Using a calibrated SEIRD model, CSP allows for the identification of the paths that drive the process during the outbreak phase and the critical transition from accelerating to decelerating growth, which serves as a reliable precursor to the epidemic peak. This framework is assessed against the 4th, 5th, and 6th waves of the COVID-19 pandemic in Greece during 2021, covering periods dominated by the Delta and Omicron variants. Using only early-stage data from short calibration windows, CSP diagnostic tools revealed distinct dynamical drivers for each wave; e.g., a transition from the 4th wave that was driven by transmission intensity (Delta variant dominance) to the 6th wave that was driven by rapid exposure-to-infection turnover and reduced opposition from recovery mechanisms (Omicron variant dominance). Furthermore, it is demonstrated that the timing of outbreak’s weakening can be accurately predicted, demonstrating robustness with results obtained from longer observation windows. These findings position multiscale analysis as a powerful, pathogen-agnostic early-warning system, capable of disentangling complex epidemic mechanisms and assessing intervention efficacy in real-time.

Article
Medicine and Pharmacology
Epidemiology and Infectious Diseases

Galina A. Eroshenko

,

Alina N. Balykova

,

Levon A. Karapetyan

,

Lyubov M. Kukleva

,

Ekaterina A. Naryshkina

,

Nadezhda S. Chervyakova

,

Yaroslav M. Krasnov

,

Konstantin S. Shevchenko

,

Vladimir V. Kutyrev

Abstract: Based on phylogenetic analysis of whole-genome sequencing of Yersinia pestis 2.MED1 strains of the medieval biovar, combined with epizootic, epidemiological, and climatic data over a 100-year period, we have reconstructed the spread of plague in Eastern Europe and Central Asia (EECA) in the 20th and 21st centuries. The data suggest the important role of three great lakes—the Caspian, Aral, and Balkhash—in the spread and preservation of Y. pestis 2.MED1 in EECA. Three waves of Y. pestis 2.MED1 spread have been identified: Caspian (Caspian Sea region foci, 1912-1945; Caucasus, 1953-1986), North Aral (Northern Aral Sea region foci, 1945-1959; Caspian Sea region foci, 1945-2015; Pre-Caucasus, 1999-2003; Karakum, 1949-1965) and Central Asian (Kyzylkum, 1924, 1983-2020; Balkhash foci, 1939-2020; Northern Aral Sea region foci, 1967-2020; Eastern Caspian Sea region foci, 1968-1985). Favorable climatic conditions in the Caspian Sea region, the Northern Aral Sea region, and the Balkhash region in the 20th and 21st centuries contributed to the rapid formation of stable natural plague foci and the long-term persistence of Y. pestis 2.MED1 strains of the medieval biovar, with their sporadic spread into other foci of EECA. Periodic introductions of the pathogen are one of the reasons for the plague re-emergence and activation of plague foci in the EECA region.

Article
Medicine and Pharmacology
Epidemiology and Infectious Diseases

Rosa Katia Bellomo

,

Maria Assunta Donato

,

Vito Cerabona

,

Teresa Esposito

,

Alessia Perna

,

Giuliana Federico

,

Carmine Guarino

,

Anna Odone

,

Michele Sparano

,

Romina Sezzatini

+4 authors

Abstract: Background: The epidemiological alert about the possible spread of different pathogens has highlighted the risk of in-ternational travelers contracting infectious diseases when visiting endemic areas. The role of travelers in disease trans-mission underscores the importance of pre-travel consultations, which provide critical information on health risks, vac-cinations, and preventive measures. Understanding travelers’ risk perceptions and behaviors is essential for enhancing global health security in the post-pandemic era. Methods: A cross-sectional study (June 2023 – January 2024) was con-ducted by administering an anonymous questionnaire at the Rome-Fiumicino Airport International Prophylaxis Clinic (USMAF-SASN). The questionnaire explored demographics, travel patterns, risk perceptions, vaccination behaviors, and sources of health information. Descriptive statistics, and a multivariable logistic regression analysis were performed to identify low-risk perception predictors. Results: Among 217 participants, 89.8% were Italian, with a balanced represen-tation of genders. The primary purpose of travel was tourism (61.6%), followed by work-related trip (23.1%). While 77.1% rated preventive measures as effective, 23.2% evaluated infection risk as low. In particular, these last were in the majority male (OR 3.68, p=0.009), teacher (OR 9.85, p=0.025), and hotels users (OR 5.96, p< 0.001). As expected, healthcare professionals and individuals using institutional health sources showed a higher risk awareness. Vaccina-tion uptake at the Airport Clinic was motivated by self-protection, vaccine confidence, and poor time flexibility to access local vaccination services, and last-minute plans, making the airport a more convenient option. Conclusions: Travelers’ risk perception is influenced by gender, profession, accommodation type, and information sources. Public health strate-gies should enhance health literacy, promote pre-travel consultations, and improve access to preventive services. Strengthening collaborations between health authorities, educational institutions, and the travel sector is key to mitigat-ing health risks and ensuring global health security. Future interventions should address structural vaccination barriers and improve outreach to under-informed travelers.

Article
Medicine and Pharmacology
Epidemiology and Infectious Diseases

Demetris Epaminondas

,

Stella Mazeri

,

Maria Lyraki

,

Christine Tait-Burkard

,

Danielle Gunn-Moore

,

Stavroula Loukaidi

,

Efstathia-Evangelia Georgiadi

,

Stavros Loizides

,

Demetris Demetriou

,

Zoe Polizopoulou

+2 authors

Abstract: In 2023, Cyprus experienced a large-scale epizootic of feline infectious peritonitis (FIP) temporally associated with the emergence of a novel feline coronavirus, FCoV-23. While molecular investigations have elucidated the recombinant origin of FCoV-23, field-based clinical and other epidemiological data from FIP cases reported during the epizootic period were needed to better characterize the outbreak. A prospective study was conducted using a structured 31-item questionnaire embedded in veterinary management software to characterize FIP cases diagnosed during the epizootic period (late 2022–2025). Data were voluntarily submitted by registered veterinarians across Cyprus. Cases were included based on a clinical diagnosis of FIP; virological confirmation of FCoV-23 infection was not required for inclusion. Data from 68 FIP cases reported by 22 clinics (response rate 21.0%) were analyzed. Affected cats were older than typically reported for FIP (mean age 3.9 years; median 3.0; range 0.4–12.9 years; SD 3.41). Most cases were documented in Limassol (51.5%) and Nicosia (25.0%). The most frequently reported clinical signs were non-specific like anorexia (60.3%) and weight loss (54.4%), while a variety of neurological and mental manifestations was documented in 35.3% of cases. An albumin-to-globulin ratio &lt;0.8 was observed in 86.8% of tested cats. Antiviral therapy (GS-441524 or molnupiravir) was administered in 92.2% of cases, with reported clinical improvement in 88.9%. These findings demonstrate the value of questionnaire-based surveillance in documenting outbreak-associated FIP patterns. Although individual cases were not uniformly confirmed as FCoV-23 infections, the increased proportion of neurological presentations among FIP cases reported during the epizootic period supports previous molecular evidence suggesting that neurological involvement was associated with FCoV-23 circulation.

Review
Medicine and Pharmacology
Epidemiology and Infectious Diseases

Hien Thi Thu Nguyen

,

Tuong Khanh Bui-Nguyen

,

Chi Que Nguyen

,

Hanh Thi My Dinh

,

Trang Khanh Tran

,

Nhung Thi Thu Hoang

,

Huong Minh Nguyen

,

Vang Le-Quy

,

Alexei Korobitsyn

,

Linh Nhat Nguyen

Abstract:

Background: Tuberculosis (TB) remains a major global cause of morbidity and mortality. Current tools for monitoring treatment response rely on sputum-based microscopy and culture, which may be insensitive, time-consuming, and impractical in extrapulmonary or pediatric TB and in individuals unable to produce sputum. Metabolomics has emerged as a promising approach to identify host-derived biomarkers reflecting treatment-associated immunometabolic changes, but evidence remains heterogeneous and incompletely synthesized. Methods: We conducted a comprehensive literature review of metabolomic biomarkers associated with TB treatment response. PubMed, Scopus, and Web of Science were searched for human studies evaluating targeted or untargeted metabolomics (NMR, LC-MS, GC-MS, CE-MS) in relation to treatment response or outcomes. Two reviewers independently screened studies, extracted data, and assessed risk of bias using QUIPS and PROBAST. Findings were synthesized using a structured framework across treatment stages and outcomes. Results: Of 218 records identified, 139 titles/abstracts were screened and 42 full texts assessed; 15 studies met inclusion criteria. Recurrent signals involved amino acid metabolism, particularly the tryptophan–kynurenine pathway, and vitamin/cofactor metabolites (pyridoxate, nicotinamide, trigonelline). Plasma studies frequently reported lipid remodeling and bile acid perturbations, while urine studies highlighted polyamine metabolism (e.g., N¹,N¹²-diacetylspermine) and fatty acid β-oxidation markers. Common limitations included inadequate adjustment for confounders and, in prediction models, small sample sizes and limited external validation. Conclusions: Metabolomic reveals reproducible but heterogeneous immunometabolic changes during TB therapy. Key pathways include tryptophan-kynurenine metabolism, vitamin/cofactor metabolism, lipid remodeling, and urine polyamine pathways. Standardization and prospective multicenter validation are needed for clinical translation.

Article
Medicine and Pharmacology
Epidemiology and Infectious Diseases

A. Perrella

,

P. Di Micco

,

U. Trama

,

P. Salvatore

,

A. Di Spirito

,

C. Tiberio

,

M. Bernardo

,

N. Capoluongo

,

G. Di Flumeri

,

R. Boenzi

+1 authors

Abstract: Background: The antimicrobial resistance crisis is driven by antibiotic overuse, often due to the difficulty in distinguishing bacterial from viral infections. While Point-of-care C-Reactive Protein (CRP) testing aids in this differentiation, its diagnostic accuracy is frequently compromised by chronic inflammatory comorbidities that elevate baseline CRP levels.Objective: This study evaluated the diagnostic utility of CRP in an Emergency Department (ED) cohort and validated a novel “Comorbidity Confounder Score” (CCS) to identify patient subgroups in whom CRP retains high diagnostic value.Methods: We conducted a retrospective cohort study of 92 patients presenting to a tertiary ED with acute flu-like symptoms between 2023 and 2025. Microbiological diagnoses were confirmed using culture and PCR. The diagnostic performance of CRP (Area Under the Curve - AUC) was assessed in the total cohort and stratified into “Low-Utility” (high comorbidity, CCS $\ge$ 2) and “High-Utility” (low comorbidity, CCS < 2) subgroups.Results: In the unselected total cohort, CRP demonstrated poor diagnostic utility (AUC = 0.61). However, stratification revealed significant divergence. In the “Low-Utility” group, CRP had no diagnostic value (AUC = 0.52). Conversely, in the “High-Utility” group, CRP performance improved markedly (AUC = 0.84).Conclusion: The diagnostic value of CRP in unselected ED patients is clinically insufficient due to confounding comorbidities. Applying the CCS algorithm effectively identifies specific patient populations for whom CRP testing remains a reliable diagnostic tool.

Article
Medicine and Pharmacology
Epidemiology and Infectious Diseases

Tsuguto Fujimoto

,

Miki Ogi

,

Kazuhiro Kitakawa

,

Takako Sano

,

Yorihiro Nishimura

,

Kouichi Kitamura

,

Minami Kikuchi Ueno

,

Minetaro Arita

Abstract: Molecular typing of enteroviruses (EVs) is essential for surveillance of hand, foot, and mouth disease (HFMD). Conventional reverse-transcription polymerase chain reaction (RT-PCR) targeting the VP4–VP2 region can be insufficiently sensitive, reducing the detectability of Enterovirus A (EV-A). We developed a single-round RT-PCR assay using a modified reverse primer design (C3R) for rapid EV detection and genotyping. Sensitivity was evaluated using EV-A71 and poliovirus type 1 reference strains and 60 EV-positive clinical specimens. The C3R-based assay showed ~1,000-fold higher sensitivity for EV-A71 than conventional assays (limit of detection: 6.6 copies/reaction). It detected 100% (60/60) of clinical specimens, whereas the conventional assay detected only 45.0% (27/60) and failed at cycle threshold (Ct) values >30. Our assay maintained 100% sensitivity even at low viral loads (Ct > 35; P < 0.0001). All amplicons yielded high-quality sequences for definitive genotyping. This C3R-based RT-PCR overcomes sensitivity limitations of existing protocols and provides reliable genotyping from low-copy specimens, supporting its use in routine diagnostics and large-scale HFMD surveillance.

Article
Medicine and Pharmacology
Epidemiology and Infectious Diseases

Rafael Zaragoza

,

Ángel Estella

,

Xavier Nuvials

,

Mireya Robles-Plaza

,

Araceli Casado-Gómez

Abstract: Background: The objective was to identify management strategies of IFI in critically ill patients through a Spanish national survey. Methods: A cross-sectional multicentre survey among ICU specialist, experienced in IFI was performed (22-April-25-July 2024). The survey consisted of 13 questions with four closed answers. Results: Sixty-three experts from 51 hospitals of 16 regions completed the survey. 95% stated that, in high-risk patients with clinical suspicion of Pulmonary Aspergillosis (PA), request galactomannan in BAL to initiate treatment. In the treatment of patients with PA and influenza, 86% declared that isavuconazole and liposomal amphotericin B are recommended treatments and in high suspicion of aspergillus coinfection, 76% recommended empirical treatment waiting for microbiological confirmation. 90% declared that the use of Extracorporeal Membrane Oxygenation (ECMO) and Renal Replacement Therapies (RRT) could be associated with lower azole levels. Regarding intraabdominal candidiasis, 78% that physiopathological changes in critically ill patients, reduce their entry into the peritoneal fluid. Conclusion: The majority of the experts agreed (>80%) on: In suspicion of PA, Galactomannan in BAL to guide treatment is mandatory; In case of aspergillosis and influenza, isavuconazole and liposomal amphotericin B are the recommended treatments; The use of ECMO and RRT could be associated with lower azole levels.

Hypothesis
Medicine and Pharmacology
Epidemiology and Infectious Diseases

Amr Ahmed

,

Sharifa Rodaini

Abstract: Background: Tumor necrosis factor-alpha (TNF-α) inhibitors have transformed the management of chronic inflammatory diseases, yet they impose a substantially elevated risk of tuberculosis (TB) reactivation—up to 25-fold depending on the agent used. This risk is principally driven by disruption of granuloma architecture and suppression of interferon-gamma (IFN-γ)–dependent macrophage bactericidal activity. Current prophylactic strategies rely predominantly on isoniazid chemoprophylaxis, which carries hepatotoxicity risks and compliance challenges. There remains an unmet need for adjunctive immunomodulatory approaches that can selectively bolster anti-mycobacterial immunity without exacerbating the underlying autoimmune condition. Hypothesis: We propose that low-dose hydroxychloroquine (HCQ), administered concomitantly with TNF-α inhibitor therapy, can serve as a targeted immunomodulatory prophylactic strategy against TB reactivation. This hypothesis is grounded in recent single-cell transcriptomic evidence demonstrating that HCQ selectively upregulates IFNG expression and cytotoxicity-associated gene programs (GZMA, GZMB, PRF1, NKG7) in effector CD8+ T cells while simultaneously reducing the dysfunctional CD38+ CD8+ T cell subset. We posit that this CD8+ T cell–mediated IFN-γ augmentation can partially compensate for the TNF-α inhibitor–induced deficit in the IL-12/IFN-γ axis, thereby preserving granuloma integrity and macrophage mycobactericidal function. Evidence Synthesis: We integrate mechanistic data from immunology, pharmacology, and TB pathogenesis to construct a multi-layered rationale. We examine the dose-dependent immunomodulatory effects of HCQ, the differential impact of TNF-α inhibitors on mycobacterial immunity, and the critical role of IFN-γ in phagosome maturation and granuloma maintenance.Conclusion: This hypothesis establishes a mechanistically grounded framework for repurposing HCQ as adjunctive TB prophylaxis in the anti-TNF setting. We propose a phased translational research program to evaluate this novel immunomodulatory strategy.

Article
Medicine and Pharmacology
Epidemiology and Infectious Diseases

Salvador Domènech-Montoliu

,

Óscar Pérez-Olaso

,

Diego Sala-Trull

,

Paloma Satorres-Martinez

,

Laura López-Diago

,

Isabel Aleixandre-Gorriz

,

Maria Rosario Pac-Sa

,

Manuel Sánchez-Urbano

,

Cristina Notari-Rodriguez

,

Juan Casanova-Suárez

+6 authors

Abstract: Background and Objective: After a SARS-CoV-2 infection, a Long COVID (LC) syndrome occurred in a high proportion of patients with affecting their health. Estimating the incidence, risk and protective factors of LC was the aim of our study. Material and Methods: We performed a prospective population-based cohort study on the Borriana COVID-19 cohort (Castellon province, Valencia Community, Spain) from May 2020 to August 2023 with a follow-up of 40 months, and considering the LC definition from the World Health Organization. We used inverse probability weighted regression. Results: With a response rate of 63.8% of a total of 722 participants, the average age was 37.7±17.4 years with 460 (62.3%) females, 644 had suffered a SARS-CoV-2 infection, and 184 suffered LC with a cumulative incidence of 28.6%. A total of 135 patients with LC remained affected, and a death associated with the syndrome occurred in 0.54% of them. Significant risk factors for LC were older age, female, chronic disease, SARS-CoV-2 exposure, reinfections and severity. Asymptomatic cases and SARS-CoV-2 vaccinations were significantly protective factors. Conclusions: A high incidence of LC was found with low recovery rate, and several risk and protective factors. Continued follow-up for non-recovered LC patients, surveillance of infections, and a SARS-CoV-2 vaccination for an at-risk population can be recommended.

Article
Medicine and Pharmacology
Epidemiology and Infectious Diseases

Vanya Rangelova

,

Dejan Jakimovski

,

Magdalena Baymakova

,

Meri Hristamyan

,

Martina Moskova

,

Sara Sariyan

,

Ilia Tsachev

,

Ani Kevorkyan

Abstract: Mpox re-emerged as a global public health concern during the 2022 international out-break, underscoring the necessity of preparedness among future healthcare professionals. This study sought to evaluate knowledge and attitudes toward Mpox among medical students in Bulgaria and North Macedonia. A cross-sectional, online survey was con-ducted from May to September 2022 among undergraduates attending medical universi-ties in both nations. The questionnaire evaluated demographic variables, knowledge of Mpox, and attitudes toward conspiracy theories associated with the emerging infectious disease. A total of 1,313 students participated, with a mean age of 22.6 ± 4.4 years and 63.7% being female. While 56.3% of respondents were familiar with Mpox, hardly 16.9% indicated having received formal or specialized information regarding the disease. Signif-icant information deficiencies were observed: merely 38.1% accurately acknowledged that antibiotics are ineffective against Mpox, and 25.0% were knowledgeable of the availability of vaccinations for prophylaxis. Common misconceptions regarding transmission and resemblances to other vesicular illnesses were prevalent. Attitudinal research indicated significant uncertainty and partial support for conspiracy theories concerning new path-ogens. The findings reveal inadequate readiness among prospective healthcare workers and highlight the necessity to enhance medical education on emerging infectious illnesses to facilitate early detection, risk communication, and epidemic preparedness in South-eastern Europe.

Article
Medicine and Pharmacology
Epidemiology and Infectious Diseases

José Oñate-Gutiérrez

,

Carlos Alvarez-Moreno

,

Claudia Cañadas-Aragón

,

Hernán Vergara-Samur

Abstract: Invasive candidiasis is a severe opportunistic infection whose incidence may be influenced by major disruptive events. The COVID-19 pandemic substantially altered hospital dynamics in Colombia. This study aimed to evaluate temporal trends, seasonality, and potential changes in the incidence of invasive candidiasis between 2019 and 2024. We conducted an observational time-series study using confirmed cases of invasive candidiasis from medium- and high-complexity hospitals in three major Colombian cities. Cases were aggregated quarterly. An interrupted time-series (ITS) analysis was performed. A total of 1,294 cases were analyzed. An increasing trend was observed until mid-2022, followed by a decline during 2023. Seasonal decomposition revealed persistent seasonality with recurrent peaks in the second and fourth quarters. The ITS analysis did not demonstrate statistically significant changes in level or slope after the interruption (p &gt; 0.05), although clinically relevant fluctuations were observed. No significant differences in temporal trends were identified across Candida species. Invasive candidiasis in Colombia exhibited a complex temporal evolution during and after the COVID-19 pandemic characterized by sustained seasonality and an increase followed by a decline. Although the ITS analysis did not identify statistically significant post-pandemic changes, the findings support the use of time-series models as valuable tools for epidemiological surveillance and trend monitoring.

Article
Medicine and Pharmacology
Epidemiology and Infectious Diseases

Mahmud Azbida

,

Sana Ferjani

,

Omar Elahmer

,

Rmadhan Osman

,

Salem Shenaisheh

,

Amal Barakat

,

Salma Abid

,

Adem Eljerbi

,

Abdulwahab Kammon

,

Haider El-Saeh

+2 authors

Abstract: Influenza sentinel surveillance in Libya was formally established in 2022 by the Libyan National Center for Disease Control (NCDC), initially comprising a single sentinel site in Tripoli. By the end of 2025, the network had expanded to 15 sites across five cities nationwide. Between 2022 and 2024, a total of 1,864 nasopharyngeal specimens were collected from patients presenting with influenza-like illness and tested using the GeneXpert for influenza A virus, influenza B virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and respiratory syncytial virus (RSV). Influenza A virus was detected in 21.1% (393/1,864) of samples and influenza B virus in 5.4% (100/1,864). SARS-CoV-2 and RSV were identified in 11.6% (216/1,864) and 4.1% (77/1,864) of specimens, respectively. A subset of 29 influenza A–positive samples was randomly selected for confirmatory testing and further molecular characterization. Real-time RT-PCR subtyping identified 13 A(H1N1)pdm09 and five A(H3N2) viruses. Whole-genome sequencing was successfully performed for 13 isolates, followed by phylogenetic analysis. Genetic characterization revealed that all A(H1N1)pdm09 viruses belonged to clade 6B.1A.5a.2a (5a.2a), while A(H3N2) viruses clustered within clade 3C.2a1b.2a.2a.3a.1 (2a.3a.1) based on hemagglutinin gene mutations. No neuraminidase mutations associated with antiviral resistance were detected. This study represents the first molecular and phylogenetic characterization of circulating human influenza viruses in Libya, with sequence data submitted to the Global Initiative on Sharing All Influenza Data (GISAID). These findings establish baseline genetic data for influenza viruses in Libya and support the strengthening of national respiratory virus surveillance.

Article
Medicine and Pharmacology
Epidemiology and Infectious Diseases

Ninel Iacobus Antonie

,

Vlad Alexandru Ionescu

,

Gina Gheorghe

,

Crista-Loredana Tiuca

,

Camelia Cristina Diaconu

Abstract:

Background/Objectives: Antimicrobial resistance (AMR) remains a major global health threat, strengthening the case for antimicrobial stewardship that limits unnecessary broad-spectrum empiric therapy while preserving timely coverage in severe infection. Large language models (LLMs) are being explored for decision support, but require rigorous offline evaluation before any clinical implementation. Methods: Single-center retrospective paired evaluation at Clinical Emergency Hospital of Bucharest (Internal Medicine, 2020–2024). The unit of analysis was the admission (N = 493), with paired 24 h empiric regimens (clinician-prescribed vs post hoc LLM-recommended via OpenAI API; not visible to clinicians; no influence on care). Local laboratory-derived epidemiology was precomputed from microbiology exports and provided as structured prompt context to approximate information parity with clinicians’ implicit local ecology knowledge. Primary (prespecified) endpoint: any contextual guardrail violation (unjustified carbapenem/antipseudomonal/anti-MRSA under prespecified structured severity/MDR-risk rules), exact McNemar. Key secondary (prespecified): Δ contextual guardrail penalty (LLM − Clin), sign test and Wilcoxon signed-rank (ties reported). Ethics committee approval was obtained. Results: Guardrail violations occurred in 17.0% of clinician regimens vs 4.9% of LLM regimens (paired RD −12.2%; matched OR 0.216, 95% CI 0.127–0.367; McNemar exact p = 1.60 × 10⁻¹⁰). Δ penalty had median 0 with 398/493 ties; among non-ties, improvements (Δ < 0) exceeded adverse shifts (79 vs 16; sign-test p = 3.47 × 10⁻¹¹). Conclusions: In this offline, non-interventional paired evaluation, LLM regimens were associated with fewer prespecified contextual guardrail violations compared to clinician empiric regimens under a rule-based stewardship benchmarking framework. These endpoints strictly quantify concordance with stewardship constraints rather than patient outcomes, necessitating cautious interpretation of secondary and subset analyses. Ultimately, reproducible guardrail-based benchmarking may support subsequent prospective, safety-governed evaluations.

Hypothesis
Medicine and Pharmacology
Epidemiology and Infectious Diseases

Amr Ahmed

Abstract:

Despite the availability of antibiotics, pulmonary tuberculosis (TB) remains a leading infectious cause of mortality globally. Treatment failure and the emergence of drug-resistant strains are largely driven by the heterogeneous architecture of caseating granulomas and the complex biophysical mechanisms by which Mycobacterium tuberculosis (Mtb) evades host immunity. Highly lipophilic frontline drugs, such as bedaquiline and clofazimine, exhibit severe sequestration within the lipid-rich necrotic caseum, preventing them from reaching the dormant persister bacilli at the lesion's core.4 Furthermore, recent biophysical discoveries reveal that Mtb utilizes extracellular vesicles and specialized lipids to mechanically stiffen host macrophage membranes, thereby arresting phagosome-lysosome fusion.6 This review proposes an AI-optimized, "Trojan Horse" hybrid nanocarrier strategy—comprising a lipidic core, a mucoadhesive chitosan shell, mannose-targeted ligands, and pH-responsive release mechanisms—to bypass these dual barriers.8 By bridging lesion-centric pharmacokinetics (fu_caseum , Deff), novel bioorthogonal diagnostic probes, and machine learning formulation designs, we present a translational roadmap aimed at achieving complete sterilization of caseous cavities.4

Review
Medicine and Pharmacology
Epidemiology and Infectious Diseases

Alfonso J. Rodriguez-Morales

,

Katherine Acevedo-Jimenez

,

María Eugenia Guevara

,

Alicia Chang-Cojulun

,

José Brea-Del Castillo

,

Melissa Palmieri

,

Maria L. Avila-Agüero

,

Francisco Javier Membrillo de Novales

,

Carlos Torres-Martínez

,

Sandra X. Olaya

+38 authors

Abstract: Yellow fever remains a major public health threat in endemic and re-emerging regions of Africa and South America, with recent outbreaks highlighting persistent gaps in prevention and surveillance. Pregnant women represent a particularly vulnerable population, yet the epidemiology, clinical impact, and preventive strategies for yellow fever in pregnancy are insufficiently characterized. Physiological and immunological changes during gestation may increase susceptibility to severe disease and contribute to adverse maternal and fetal outcomes, including miscarriage, stillbirth, preterm birth, and, in rare cases, perinatal transmission. Diagnostic challenges, overlapping clinical presentations with other arboviral and hepatic diseases, and limited access to specialized care further complicate clinical management in many endemic settings. This perspective provides a comprehensive overview of yellow fever in pregnancy during the 2024–2026 outbreak in the Americas, including a risk-stratification framework for prevention. We summarize current evidence on epidemiology, pathophysiology, diagnosis, and supportive care, and examine prevention strategies with particular emphasis on vaccination. Accumulated observational evidence and substantial real-world experience have not demonstrated an increased risk of serious adverse events and generally support the effectiveness of yellow fever vaccination during pregnancy when administered with appropriate clinical judgment. In high-risk settings, the benefits of maternal immunization clearly outweigh theoretical concerns, supporting a flexible, risk-based approach, despite relatively limited evidence. We also discuss national and international policies, post-pregnancy booster recommendations, and the importance of integrating vaccination assessment into antenatal care. Finally, we highlight critical knowledge gaps and research priorities, including the need for prospective registries and strengthened pharmacovigilance. Coordinated clinical and public health strategies are essential to protect maternal and neonatal health and to reduce the burden of yellow fever in endemic and re-emerging settings.

Article
Medicine and Pharmacology
Epidemiology and Infectious Diseases

Itzel Elizabeth Garibay-Padilla

,

Jorge Eduardo Hernandez-Del Rio

,

Dayana Estefania Orozco-Sepulveda

,

Christian Gonzalez-Padilla

,

Tomas Miranda-Aquino

,

Vanessa Salas-Bonales

,

Judith Carolina De Arcos-Jimenez

,

Jaime Briseno-Ramirez

Abstract: Background/Objectives: Infective endocarditis (IE) carries substantial mortality, particularly in middle-income settings where patient profiles and microbial ecology differ from those of cohorts used to derive international prognostic scores. Syndrome-specific, locally grounded decision aids for empirical therapy are also scarce. We aimed to identify predictors of in-hospital mortality, externally evaluate the RiskE and ICE scores, and construct a Bayesian weighted-incidence syndromic combination antibiogram (WISCA) for IE. Methods: We conducted a retrospective cohort study of consecutive adults with definite or possible IE admitted between January 2019 and January 2026. Candidate predictors were screened in two phases and a clinically specified model was estimated with maximum-likelihood and Firth penalization, with 1000-replicate bootstrap optimism correction. Discrimination was compared against RiskE and ICE using DeLong’s test and reclassification metrics. For empirical coverage, we built a WISCA using identified pathogens, reporting both non-Bayesian bootstrap estimates and Bayesian hierarchical partial-pooling estimates with species- and antibiotic-level random intercepts; analyses were also stratified by IE type. Results: In-hospital mortality was 22.9%. Septic shock (Firth OR 9.23, 95% CI 2.40–40.61) and acute heart failure (OR 10.01, 95% CI 2.78–41.07) were the strongest independent predictors; the final model achieved an AUC of 0.922 (optimism-corrected 0.908) and outperformed RiskE (AUC 0.598) and ICE (AUC 0.632). Bayesian WISCA ranked vancomycin + gentamicin and meropenem + gentamicin highest (both 87.0%); several β-lactam–based combinations provided comparably high coverage without requiring routine carbapenems. Coverage was consistently higher for community-acquired than healthcare-associated IE. Conclusions: A simple variable model provided strong, locally valid mortality prediction and substantially outperformed international scores in this hemodialysis-predominant cohort. Bayesian WISCA offers stable, institution-specific empirical coverage estimates that can support stewardship-oriented regimen selection; multicenter validation is warranted.

Article
Medicine and Pharmacology
Epidemiology and Infectious Diseases

Lubabalo Macingwana

,

Nenekazi Masikantsi

,

Lonwabo Mbadu

,

Gugulethu Miya

,

Mathulo Shauli

,

Gabriel Mashabela

Abstract: The persistent rise of multidrug-resistant strains of Mycobacterium tuberculosis necessitates a continued search for new potent drugs. Plants are a great source of therapeutic agents; the challenge is finding these therapeutic plants. Wild Baboons are self-sufficient animals that can find edible and non-nutritive plants for therapeutic purposes. Therefore, the excreta from the wild baboons will likely contain therapeutic agents. This study investigates the presence of antimycobacterial agents in wild ba-boon feces. Faecal samples were collected randomly from the forest, and ethanol and hydro-distillation extracts were prepared. The qualitative screening was performed using reagent tests. Quantitative analysis was conducted using GC-MS. Antimycobacterial testing was conducted using Mycobacterium smegmatis as a surrogate for Mycobacterium tuberculosis, and Microplate Alamar Blue Assay screening technique was employed. The qualitative screening showed the presence of Tannins, alkaloids, glycosides, phenolics, terpenoids, flavonoids, and steroids. Essential oils obtained from hydro-distillation were analyzed with GC-MS, and 26 compounds were quantified, including α-pinene, limonene, eucalyptol, and 2-Pentylfuran. Essential Oils showed activity at 0,5 mg/ml and ethanol extract at 2 mg/mL when tested against M. smegmatis. This study demonstrates that wild baboon feces contain biologically active plant secondary metabolites. Also, the findings of this study could be used to develop new effective anti-Mycobacterium tuberculosis agents to improve the lives of humankind.

Review
Medicine and Pharmacology
Epidemiology and Infectious Diseases

Hien Thi Thu Nguyen

,

Vang Le-Quy

,

Anh Tuan Dinh-Xuan

,

Linh Nhat Nguyen

Abstract: Background: Artificial intelligence (AI) is increasingly used to support tuberculosis (TB) screening and diagnosis, especially computer-aided detection (CAD) applied to chest radiography (CXR). The value of these programs depends not only on diagnostic accuracy but also on threshold calibration, integration into clinical workflow, and capacity for confirmatory testing. Methods: We conducted a narrative state-of-the-art review of AI applications relevant to TB screening and diagnosis. We synthesize evidence from World Health Organization policy documents, independent validation initiatives, and peer-reviewed studies re-porting diagnostic performance and real-world implementation outcomes. Results: CAD for CXR is the most mature AI application and is recommended by WHO for TB screening and triage among individuals aged ≥15 years in specific contexts. CAD-CXR can achieve sensitivity comparable to human readers, although performance varies by product, software version, population, and imaging conditions. Threshold selection is therefore a programmatic decision influencing referral volume and resource use. Inde-pendent benchmarking and local verification studies are essential to confirm performance and assess subgroup variability, including among people living with HIV and those with prior TB. Other AI approaches, including computed tomography (CT)-based imaging analysis, point-of-care ultrasound interpretation, cough or stethoscope sound analysis, clinical risk models, and genomic resistance prediction, are still at earlier stages and generally require further independent validation before routine programmatic use. Conclusions: AI has the potential to strengthen TB screening and diagnostic pathways, but impact should be evaluated using patient- and program-level outcomes rather than accuracy alone. Responsible scale-up requires local calibration, governance safeguards, and ongoing monitoring in real-world settings.

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