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Biomedicines
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Pathogenesis, Diagnosis and Treatment of Infectious Diseases
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Pathogenesis, Diagnosis and Treatment of Infectious Diseases

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (31 August 2025) | Viewed by 6481

Special Issue Editor

Dr. Laura Franza

E-Mail Website
Guest Editor
Department of Emergency Medicine, Fondazione Policlinico Universitario, Università Cattolica del Sacro Cuore, 00168 Roma, Italy
Interests: inflammation; microbiota; immunology; sepsis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Infectious diseases are a major global health challenge, in particular in a modern world that face challenges of emerging pathogens, antimicrobial resistance, and evolving epidemiological patterns.

This special issue of Biomedicines aims to provide a comprehensive exploration of the mechanisms underlying infectious diseases, novel diagnostic approaches, and cutting-edge therapeutic strategies.

We welcome contributions that enhance our understanding of microbial pathogenesis, host immune responses, and pathogen-host interactions. Submissions focusing on innovative diagnostic techniques, including molecular, immunological, and imaging-based methods, research on antimicrobial agents, novel drug delivery systems, vaccine development, and personalized treatment strategies are all encouraged. Papers exploring the evolving epidemiology of infective diseases, particularly considering the role of underlying chronic diseases, a very important topic in our aging society, will also be gladly considered. We also hope to receive submission concerning changing epidemiology and novel microbial pathogens emerging in the context of climate change.

By bringing together research and reviews from experts in microbiology, immunology, clinical medicine, and biomedical sciences, this special issue aims to advance knowledge and improve outcomes in the fight against infectious diseases.

Dr. Laura Franza
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • infection
  • infectious diseases
  • vaccination
  • antibiotics
  • antibiotic resistance
  • novel therapies
  • novel diagnosis
  • inflammaging
  • immunosenescence

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Related Special Issue

Published Papers (8 papers)

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Research

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15 pages, 519 KB  
Article
Detection of Viruses with Oncogenic and Oncomodulatory Potential in Head and Neck Tumors—External Auricle
by Kalina Shishkova, Ivo Sirakov, Stoyan Shishkov, Elena Tasheva-Terzieva, Stefan Dimitrov Gergov, Zornitsa Tileva, Reneta Dimitrova, Ivailo Alexiev and Raina Gergova
Biomedicines 2025, 13(10), 2339; https://doi.org/10.3390/biomedicines13102339 - 25 Sep 2025
Viewed by 377
Abstract
It is estimated that approximately 90% of all head and neck cancers are squamous cell carcinomas with a complex and multifactorial etiology. Molecular and epidemiological studies provide evidence for the role of oncogenic viruses in the initiation and/or oncomodulation of head and neck [...] Read more.
It is estimated that approximately 90% of all head and neck cancers are squamous cell carcinomas with a complex and multifactorial etiology. Molecular and epidemiological studies provide evidence for the role of oncogenic viruses in the initiation and/or oncomodulation of head and neck squamous cell carcinoma. Objectives: The present study aimed to detect the presence of high- and low-risk HPV, BKPyV, EBV, HCMV, HSVs in biopsy samples of squamous cell carcinoma of the external auricle in patients in Bulgaria. Materials and Methods: The study included 41 biopsy specimens from etiologically undiagnosed cases of squamous cell carcinoma of the external auricle. Molecular biological methods were used to detect the viruses—conventional and nested PCR, and sequence analysis. Results: The results obtained showed that none of the samples were found to have a high-risk HPV genotype. The highest percentage of samples showed genotype 6/11, and the lowest number of samples showed low-risk genotype 44. Of all herpesviruses, EBV was found in the largest proportion of samples, being present in the sample as a co-infection with HPV and always together with genotype 6/11. The frequency distribution, as a percentage and number of samples, of the possibilities for co-infection of EBV with each of the HPV genotypes was established. Of the remaining herpesviruses, the presence of HSV 2 was not confirmed in any of the samples. HSV 1 was present in only three of the samples, as a co-infection with genotypes 6/11, 42 and 43. When examining the samples for the presence of HCMV, only one positive sample was found, with both HPV 6/11 and 42 additionally present in the sample. Conclusions: For the first time, HPV, BKPyV, EBV, HCMV and HSVs were investigated and their possible involvement alone or as co-infection in the carcinogenesis of squamous cell carcinoma of the external auricle in patients in Bulgaria. The presence of the mentioned viruses, as well as the non-random distribution of EBV + HPV 6/11 and EBV + HPV 44, proven by us, does not necessarily make them etiological agents, but they could, through different and known mechanisms, influence the initiation and/or modulation of carcinogenesis. Full article
(This article belongs to the Special Issue Pathogenesis, Diagnosis and Treatment of Infectious Diseases)
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17 pages, 2396 KB  
Article
Lyme-Borreliosis Disease: IgM Epitope Mapping and Evaluation of a Serological Assay Based on Immunodominant Bi-Specific Peptides
by Mônica E. T. A. Chino, Paloma Napoleão-Pêgo, Virgínia L. N. Bonoldi, Gilberto S. Gazeta, João P. R. S. Carvalho, Carlos M. Morel, David W. Provance-Jr and Salvatore G. De-Simone
Biomedicines 2025, 13(8), 1930; https://doi.org/10.3390/biomedicines13081930 - 8 Aug 2025
Viewed by 576
Abstract
Lyme borreliosis (LB) is a tick-borne infection of global relevance that remains underrecognized, hindering effective surveillance and diagnosis. This lack of awareness and the limited specificity and low antibody titters of current serological assays underscore the need for improved diagnostic tools. Here, we [...] Read more.
Lyme borreliosis (LB) is a tick-borne infection of global relevance that remains underrecognized, hindering effective surveillance and diagnosis. This lack of awareness and the limited specificity and low antibody titters of current serological assays underscore the need for improved diagnostic tools. Here, we investigated the molecular fine specificity of IgM antibody responses to five proteins of Borrelia burgdorferi. Materials and Methods: We employed peptide arrays on cellulose support (SPOT synthesis) to screen IgM epitopes and assess cross-reactivity through databank searches and Enzyme-Linked Immunosorbent Assay (ELISA). Validation was performed using ELISA and Receiver Operating Characteristic (ROC) curve analysis. Results: We identified ten IgM epitopes, of which four were classified as specific. The ELISA peptide assay demonstrated a sensitivity of ≥87.3%, specificity of ≥56.2%, and accuracy of ≥66.6%. A bi-specific peptide was subsequently synthesized and evaluated by ELISA using a panel of patient sera representing different pathologies. This result showed a sensitivity of 85.0% and a specificity of 100.0%, with significant differences in cross-reactivity between the leptospirosis and syphilis groups. Conclusions: These findings indicate that the identified peptide combinations could facilitate the development of new, highly specific serodiagnostic assays, thereby enhancing public health initiatives and epidemiological studies. Full article
(This article belongs to the Special Issue Pathogenesis, Diagnosis and Treatment of Infectious Diseases)
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14 pages, 533 KB  
Article
Immunorecovered but Exhausted: Persistent PD-1/PD-L1 Expression Despite Virologic Suppression and CD4 Recovery in PLWH
by Bogusz Aksak-Wąs, Karolina Skonieczna-Żydecka, Miłosz Parczewski, Rafał Hrynkiewicz, Filip Lewandowski, Karol Serwin, Kaja Mielczak, Adam Majchrzak, Mateusz Bruss and Paulina Niedźwiedzka-Rystwej
Biomedicines 2025, 13(8), 1885; https://doi.org/10.3390/biomedicines13081885 - 3 Aug 2025
Viewed by 703
Abstract
Background/Objectives: While ART effectively suppresses HIV viremia, many PLWH exhibit persistent immune dysfunction. This study aimed to assess immune recovery and immune exhaustion (PD-1/PD-L1 expression) in newly diagnosed versus long-term ART-treated individuals. Methods: We analyzed 79 PLWH: 52 newly diagnosed individuals (12-month follow-up) [...] Read more.
Background/Objectives: While ART effectively suppresses HIV viremia, many PLWH exhibit persistent immune dysfunction. This study aimed to assess immune recovery and immune exhaustion (PD-1/PD-L1 expression) in newly diagnosed versus long-term ART-treated individuals. Methods: We analyzed 79 PLWH: 52 newly diagnosed individuals (12-month follow-up) and 27 long-term-treated patients (Ukrainian refugees). Flow cytometry was used to evaluate CD4+ and CD8+ counts, the CD4+/CD8+ ratio, and PD-1/PD-L1 expression on CD3+, CD4+, and CD19+ lymphocytes. ART regimen and HIV subtype were included as covariates in linear regression models. Results: At 12 months, CD4+ counts were similar between groups (median 596.5 vs. 621 cells/μL, p = 0.22), but newly diagnosed patients had higher CD8+ counts (872 vs. 620 cells/μL, p = 0.028) and a lower CD4+/CD8+ ratio (0.57 vs. 1.05, p = 0.0027). Immune exhaustion markers were significantly elevated in newly diagnosed individuals: CD4+ PD-1+ T cells (24.4% vs. 3.85%, p = 0.0002) and CD3+ PD-1+ T cells (27.3% vs. 12.35%, p < 0.0001). Linear regression confirmed group membership independently predicted higher CD3+ (β = +21.92, p < 0.001), CD4+ (β = +28.87, p < 0.0001), and CD19+ (β = +8.73, p = 0.002) percentages. Lipid parameters and SCORE2 did not differ significantly. Conclusions: Despite virologic suppression and CD4+ recovery, immune exhaustion markers remain elevated in newly diagnosed PLWH, suggesting incomplete immune normalization. Traditional parameters (CD4+ count and CD4+/CD8+ ratio) may not fully capture immune status, warranting broader immunologic profiling in HIV care. Full article
(This article belongs to the Special Issue Pathogenesis, Diagnosis and Treatment of Infectious Diseases)
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11 pages, 4370 KB  
Article
Steatosis and Interferon Associated with HBsAg Immune Control in Chronic Hepatitis B: A Real-World Propensity Score-Matched Study
by Qi Xu, Junjie Chen, Bilian Yao, Xinxin Zhang and Yue Han
Biomedicines 2025, 13(7), 1538; https://doi.org/10.3390/biomedicines13071538 - 24 Jun 2025
Viewed by 656
Abstract
Background/Objectives: The baseline determinants of functional cure in chronic hepatitis B (CHB) are largely unknown. By applying propensity score matching (PSM) to real-world data, we aimed to identify traits associated with functional cure. Methods: We included CHB cases which achieved a functional cure [...] Read more.
Background/Objectives: The baseline determinants of functional cure in chronic hepatitis B (CHB) are largely unknown. By applying propensity score matching (PSM) to real-world data, we aimed to identify traits associated with functional cure. Methods: We included CHB cases which achieved a functional cure and randomly selected non-achievers from patients followed from 2000 to 2020. Initial screening of baseline candidate traits was conducted using PSM-balanced cases and controls. Subsequently, through multiple rounds of leave-one-covariate-out on the balanced cohorts, we validated the impact of these traits using survival analysis. Results: In total, 85 cases (mean age: 35.78; female/male: 23/62) were compared with 247 controls (mean age: 37.08; female/male: 80/167, out of 3666), with a median follow-up of 69.56 months. Steatosis and interferon (IFN) treatment were significantly more frequent in the cases, as confirmed by forest plots showing significant hazard ratios. During validation, whether through balancing all covariates or leave-one-covariate-out matching, both steatosis and exposure to IFN resulted in a higher number of functional cures and HBsAg seroconversions. Further comparisons revealed that add-on or monotherapy outperformed switching (from IFN to NUC), while the de novo (IFN + NUC, followed by NUC) approach was not observed. Conclusions: We confirmed that individuals with steatosis at baseline or those who received IFN were more likely to achieve HBsAg immune control, with monotherapy/add-on therapy being emphasized. Full article
(This article belongs to the Special Issue Pathogenesis, Diagnosis and Treatment of Infectious Diseases)
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9 pages, 998 KB  
Article
Enteroviral Transverse Myelitis Presenting as Acute Ataxia in Children: A Case Series
by Luka Švitek, Dominik Ljubas, Nina Krajcar, Maja Vrdoljak Pažur, Ana Tripalo Batoš, Irena Tabain, Srđan Roglić and Lorna Stemberger Marić
Biomedicines 2025, 13(6), 1492; https://doi.org/10.3390/biomedicines13061492 - 18 Jun 2025
Viewed by 627
Abstract
Background: Enteroviruses, members of the Picornaviridae family, typically cause asymptomatic or mild infections. However, they can also result in central nervous system (CNS) involvement, with transverse myelitis (TM) occurring only on rare occasions. TM is a syndrome characterized by acute or subacute [...] Read more.
Background: Enteroviruses, members of the Picornaviridae family, typically cause asymptomatic or mild infections. However, they can also result in central nervous system (CNS) involvement, with transverse myelitis (TM) occurring only on rare occasions. TM is a syndrome characterized by acute or subacute spinal cord dysfunction, leading to neurological deficits below the level of the lesion. Case report: We report a case series of eight pediatric patients admitted over a three-month period, June to August 2024. All patients presented with ataxia and/or other neurological symptoms, alongside abnormal cerebrospinal fluid (CSF) findings. Although ataxia is commonly associated with cerebellitis, magnetic resonance imaging (MRI) in this cohort revealed findings consistent with TM. Notably, all patients demonstrated similar MRI abnormalities. The onset of symptoms occurred over a short time during an enterovirus epidemic. Enteroviral RNA was detected, or the virus was isolated in seven patients, while one patient had a close epidemiological link to the virus. All patients achieved full recovery following immunomodulatory therapy. Conclusions: This case series underscores that ataxia may be an atypical symptom associated with TM. Furthermore, there was a notable distinction between the clinical presentation and neuroradiological findings. Immunomodulatory therapy with immunoglobulins and corticosteroids has been shown to be effective and safe, supporting the hypothesis of an immune-mediated pathogenesis in these patients. Full article
(This article belongs to the Special Issue Pathogenesis, Diagnosis and Treatment of Infectious Diseases)
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Review

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24 pages, 1052 KB  
Review
Recurrent Erysipelas: Clinical Challenges and Strategies for Prevention—A Narrative Literature Review
by Dominika Maria Jaskóła-Polkowska, Krystian Blok, Anna Skibińska and Andrzej Chciałowski
Biomedicines 2025, 13(10), 2448; https://doi.org/10.3390/biomedicines13102448 - 8 Oct 2025
Viewed by 418
Abstract
Recurrent erysipelas is a common and clinically significant condition that poses challenges for both patients and healthcare systems. Each episode may damage lymphatic vessels, leading to chronic lymphedema, which perpetuates the risk of further relapses. Recurrence rates remain high, ranging from 11% in [...] Read more.
Recurrent erysipelas is a common and clinically significant condition that poses challenges for both patients and healthcare systems. Each episode may damage lymphatic vessels, leading to chronic lymphedema, which perpetuates the risk of further relapses. Recurrence rates remain high, ranging from 11% in outpatients during the first year to up to 46% of hospitalized patients within three years. The lower limbs are the most frequent site, although recurrences may also occur in other regions, such as the upper limb after mastectomy with lymph node dissection. This review summarizes current knowledge on risk factors, preventive measures, and chemoprophylaxis in recurrent erysipelas. Modifiable risk factors such as obesity, diabetes, venous insufficiency, tinea pedis, and poor hygiene play an important role, while non-modifiable factors include age, sex, and a history of prior episodes. Non-pharmacological strategies—weight reduction, glycemic control, smoking cessation, compression therapy, and meticulous skin care—form the cornerstone of prevention and may reduce the need for long-term antibiotics. Antibiotic prophylaxis, most commonly with oral penicillin V or intramuscular benzathine penicillin, has been shown to lower recurrence rates. However, efficacy may be reduced in patients with chronic edema or severe obesity. Macrolides serve as alternatives in penicillin-allergic patients, but concerns remain about resistance, adverse effects, and drug–drug interactions. In conclusion, recurrent erysipelas requires a multifaceted approach. While antibiotic prophylaxis is effective, its long-term success depends on simultaneous management of underlying conditions. Further studies are needed to define optimal regimens, treatment duration, and non-antibiotic alternatives. Full article
(This article belongs to the Special Issue Pathogenesis, Diagnosis and Treatment of Infectious Diseases)
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23 pages, 994 KB  
Review
Advances in Techniques for the Structure and Functional Optimization of Therapeutic Monoclonal Antibodies
by Chenchen He, Weijin Huang, Xi Wu and Huanzhang Xia
Biomedicines 2025, 13(9), 2055; https://doi.org/10.3390/biomedicines13092055 - 23 Aug 2025
Viewed by 1149
Abstract
Monoclonal antibodies (mAbs), as potent therapeutic agents, have been widely applied in the treatment of various major diseases, including infectious diseases, autoimmune disorders, cancers, and neurodegenerative diseases. However, early-generation mAbs were limited by high immunogenicity, short half-life, and insufficient affinity, which compromised their [...] Read more.
Monoclonal antibodies (mAbs), as potent therapeutic agents, have been widely applied in the treatment of various major diseases, including infectious diseases, autoimmune disorders, cancers, and neurodegenerative diseases. However, early-generation mAbs were limited by high immunogenicity, short half-life, and insufficient affinity, which compromised their therapeutic efficacy. With technological advancements, novel approaches such as high-throughput screening and glycosyl modification have been introduced to improve the performance of mAbs. Furthermore, computer-aided design techniques—including molecular docking, molecular dynamics simulations, and artificial intelligence -based methods—are increasingly being employed to accelerate the optimization process. This review summarizes recent progress in the optimization of therapeutic mAbs, with a focus on technological breakthroughs and applications in affinity enhancement, development of broad-spectrum mAbs, specificity modulation, immunogenicity reduction, and stability improvement. Additionally, it discusses current challenges and future directions in antibody optimization. This review aims to provide insights and references for the development and optimization of next-generation antibody drugs, ultimately promoting the clinical application of safer and more effective mAb-based therapies. Full article
(This article belongs to the Special Issue Pathogenesis, Diagnosis and Treatment of Infectious Diseases)
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34 pages, 2408 KB  
Review
Multidrug-Resistant Infections and Metabolic Syndrome: An Overlooked Bidirectional Relationship
by Carlo Acierno, Riccardo Nevola, Fannia Barletta, Luca Rinaldi, Ferdinando Carlo Sasso, Luigi Elio Adinolfi and Alfredo Caturano
Biomedicines 2025, 13(6), 1343; https://doi.org/10.3390/biomedicines13061343 - 30 May 2025
Cited by 2 | Viewed by 1305
Abstract
Over the past two decades, metabolic syndrome (MetS) and infections caused by multidrug-resistant (MDR) pathogens have emerged as converging global health challenges. Traditionally investigated as separate entities, accumulating evidence increasingly supports a bidirectional relationship between them, mediated by chronic inflammation, immune dysregulation, gut [...] Read more.
Over the past two decades, metabolic syndrome (MetS) and infections caused by multidrug-resistant (MDR) pathogens have emerged as converging global health challenges. Traditionally investigated as separate entities, accumulating evidence increasingly supports a bidirectional relationship between them, mediated by chronic inflammation, immune dysregulation, gut microbiota alterations, and antibiotic-driven expansion of the resistome. This narrative review examines the complex immunometabolic interplay linking MetS and MDR infections, focusing on molecular mechanisms, clinical implications, and prospective research directions. A systematic literature search was conducted using major databases, including PubMed and Scopus, targeting studies from the last 15 years that explore the interface between metabolic dysfunction and antimicrobial resistance. Particular attention is given to key immunometabolic pathways such as the IRS–PI3K–AKT–mTOR axis; the contribution of visceral adiposity and Toll-like receptor (TLR)-mediated inflammation; and the role of gut dysbiosis in augmenting both susceptibility to infections and metabolic derangements. Evidence is presented supporting the hypothesis that MetS increases host vulnerability to MDR pathogens, while chronic MDR infections may reciprocally induce systemic metabolic reprogramming. Viral infections with established metabolic sequelae (e.g., HIV, hepatitis C virus [HCV], and cytomegalovirus [CMV]) are also considered to broaden the conceptual framework. Although current data remain largely associative and fragmented, the emerging MetS–MDR syndemic model poses substantial challenges for translational research, antimicrobial stewardship, and personalized therapeutic strategies. Recognizing this reciprocal relationship is pivotal for refining infection risk stratification, optimizing treatment, and informing public health policies. Further investigations are warranted to elucidate the magnitude and directionality of this association and to identify predictive immunometabolic biomarkers that may guide targeted interventions in high-risk populations. Full article
(This article belongs to the Special Issue Pathogenesis, Diagnosis and Treatment of Infectious Diseases)
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