Pathogens

27 pages, 3634 KB

Open AccessSystematic Review

Global Landscape of Molecular and Immunological Diagnostic Tests for Human Leishmaniasis: A Systematic Review and Meta-Analysis

by Mayron Antonio Candia-Puma, Brychs Milagros Roque-Pumahuanca, Laura Yesenia Machaca-Luque, Leydi Pola-Romero, Alexsandro Sobreira Galdino, Ricardo Andrez Machado-de-Ávila, Rodolfo Cordeiro Giunchetti, Eduardo Antonio Ferraz Coelho, Vanessa Adaui and Miguel Angel Chávez-Fumagalli

Pathogens 2025, 14(11), 1123; https://doi.org/10.3390/pathogens14111123 - 4 Nov 2025

Abstract

Background: Leishmaniasis is a serious global public health challenge. Its accurate diagnosis is essential for guiding treatment but remains complex, often requiring a combination of tests. Methods: We conducted a systematic review and meta-analysis to evaluate the applicability and diagnostic accuracy of molecular [...] Read more.

Background: Leishmaniasis is a serious global public health challenge. Its accurate diagnosis is essential for guiding treatment but remains complex, often requiring a combination of tests. Methods: We conducted a systematic review and meta-analysis to evaluate the applicability and diagnostic accuracy of molecular and immunological tests for human tegumentary (TL) and visceral leishmaniasis (VL), searching PubMed for studies published between 1990–2021. Results: Among 165 included studies, PCR-based tests showed high accuracy, with area under the curve values (AUC_FPR) of 0.919 for TL and 0.965 for VL. For TL, serological tests exhibited median sensitivities of 83.3–88.1% and specificities of 82.0–92.4%. For VL, the direct agglutination test (DAT) and ELISA demonstrated higher sensitivity (93.0–93.8%) than rapid tests (89.1%) or immunofluorescence (82.0%), all with high specificity (95.5–96.9%). DAT performance (AUC_FPR = 0.966) was comparable to molecular tests. Conclusions: Molecular tests are highly accurate for diagnosing leishmaniasis. However, their routine implementation in endemic areas is limited by the need for specialized expertise and infrastructure. We advocate for developing diagnostic procedures tailored to each endemic setting, where molecular methods could facilitate early and accurate diagnosis. Full article

(This article belongs to the Special Issue Parasitic Diseases in the Contemporary World)

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15 pages, 653 KB

Open AccessArticle

Clinical Associations and Coexistence of Polyomavirus DNAemia with EBV and CMV in Pediatric Hematology/Oncology Patients, Including HCT Recipients—A Pilot Study

by Tomasz Bogiel, Mateusz Rzepka, Dagmara Depka-Radzikowska, Patrycja Zalas-Więcek, Krzysztof Czyżewski, Monika Richert-Przygońska, Jan Styczyński, Robert Dębski, Elżbieta Grześk, Grzegorz Grześk, Piotr Kanarek and Agnieszka Krawczyk

Pathogens 2025, 14(11), 1122; https://doi.org/10.3390/pathogens14111122 - 4 Nov 2025

Abstract

Polyomaviruses (BKPyV and JCPyV) and herpesviruses (EBV, CMV) usually infect people during childhood, and may be associated, in some clinical states, with immunocompromised individuals. The aim of this study was to investigate the occurrence and coexistence of polyomavirus (BKPyV and JCPyV) and herpesvirus [...] Read more.

Polyomaviruses (BKPyV and JCPyV) and herpesviruses (EBV, CMV) usually infect people during childhood, and may be associated, in some clinical states, with immunocompromised individuals. The aim of this study was to investigate the occurrence and coexistence of polyomavirus (BKPyV and JCPyV) and herpesvirus (CMV and EBV) DNAemia in pediatric hematology/oncology patients, including HCT recipients, and to assess the clinical relevance of polyomaviruses DNAemia. Whole blood samples of 99 children (including 71 patients undergoing HCT) were analyzed for the DNA of the herpes- and polyomaviruses. Co-existence of herpesvirus DNAemia was checked for the patients and clinically analyzed in detail, especially for those positive for BKPyV DNA. BKPyV DNAemia was detected in 15 (15.2%) patients, with viral loads ranging from 1.2 × 10³–1.7 × 10⁷ DNA IU/mL. No JCPyV DNA was detected in any of the samples. Coinfections with EBV or CMV DNAemia were observed in a subset of BKPyV-positive patients. BKPyV DNAemia was more frequent among children with leukemia and in those undergoing HCT. Our findings highlight the clinical associations between BKPyV and herpesvirus DNAemia in immunocompromised pediatric patients. Routine BKPyV DNA monitoring, alongside standard herpesvirus screening, may provide clinically valuable insights in high-risk pediatric cohorts, particularly those with hematologic malignancies and post-HCT status. Full article

(This article belongs to the Section Viral Pathogens)

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12 pages, 547 KB

Open AccessArticle

Exploratory Study on Efficacy and Safety of Minocycline-Based Dual Therapy for Helicobacter pylori Eradication

by Wen Gao, Jingwen Li, Yuling Tian, Chaoyi Ge, Chi Wang, Jianxiang Liu, Yixuan Li and Hong Cheng

Pathogens 2025, 14(11), 1121; https://doi.org/10.3390/pathogens14111121 - 3 Nov 2025

Abstract

Background & Aims: This study aimed to evaluate the feasibility of vonoprazan–minocycline (VM) dual therapy for Helicobacter pylori infection. Methods: In this open-label RCT, 120 H. pylori-infected patients (60 treatment-naïve and 60 treatment-failure cases) were randomized to receive vonoprazan–amoxicillin dual therapy (VA: [...] Read more.

Background & Aims: This study aimed to evaluate the feasibility of vonoprazan–minocycline (VM) dual therapy for Helicobacter pylori infection. Methods: In this open-label RCT, 120 H. pylori-infected patients (60 treatment-naïve and 60 treatment-failure cases) were randomized to receive vonoprazan–amoxicillin dual therapy (VA: vonoprazan 20 mg b.i.d. + amoxicillin 1.0 g t.i.d., control group) or VM dual therapy (vonoprazan 20 mg b.i.d. + minocycline 100 mg b.i.d., test group) for 14 days. The primary outcome was eradication rates. Secondary outcomes included adverse effects (AEs). Results: As first-line treatment, eradication rates were 96.7% (VA) vs. 90.0% (VM) in intention-to-treat (ITT) analysis (p = 0.30) and 96.7% (VA) vs. 96.4% (VM) in per-protocol (PP) analysis (p = 0.96). For rescue treatment, eradication rates were 86.7% (VA) vs. 76.7% (VM) in ITT (p = 0.32) and 89.7% (VA) vs. 79.3% (VM) in PP (p = 0.28). Overall eradication rates were 91.7% (VA) vs. 83.3% (VM) in ITT (p = 0.17) and 93.2% (VA) vs. 87.7% (VM) in PP (p = 0.31). VM had a higher incidence of AEs than VA (30.0% vs. 10.0%, p = 0.006), with dizziness being the most common (18.3%). Conclusions: VM dual therapy was shown to be an effective and safe treatment option, demonstrating comparable eradication rates to VA dual therapy. While VM had a slightly higher incidence of AEs, they were generally mild and manageable. VM remained a valuable alternative for patients with penicillin allergies or amoxicillin resistance. Full article

(This article belongs to the Special Issue Pathogenesis, Diagnosis, and Innovative Therapies in Clinical Infections)

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8 pages, 1173 KB

Open AccessCommunication

Synovial Fluid Analysis in Melioidosis: Experiences from the Darwin Prospective Melioidosis Study

by Stuart Campbell, Tze I. Lee, Robert W. Baird, Ella M. Meumann and Bart J. Currie

Pathogens 2025, 14(11), 1120; https://doi.org/10.3390/pathogens14111120 - 3 Nov 2025

Abstract

Melioidosis is a multisystem disease caused by the sapronotic soil bacterium Burkholderia pseudomallei. Septic arthritis (SA) can occur as either a primary or secondary focus and requires surgical management with prolonged antimicrobial treatment. We used the Darwin Prospective Melioidosis Study to identify [...] Read more.

Melioidosis is a multisystem disease caused by the sapronotic soil bacterium Burkholderia pseudomallei. Septic arthritis (SA) can occur as either a primary or secondary focus and requires surgical management with prolonged antimicrobial treatment. We used the Darwin Prospective Melioidosis Study to identify patients with melioidosis and SA, filtered by culture confirmation of B. pseudomallei, and subsequently collected synovial fluid analysis, laboratory, clinical, and risk factor data. We identified 68 patients in total with a label of SA, of which 46 patients supplied 69 synovial fluid samples which were culture-positive. These most commonly came from the knee (61%) and ankle (16%), though half (54%) of the specimens were clotted and unable to undergo cell count. We found a median white cell count (WCC) of 63,000 × 10⁶ cells/L in B. pseudomallei culture-positive samples. There was a numerical, but non-significant, difference in median synovial fluid WCC when stratified by preceding antimicrobial use (90,000 × 10⁶ cells/L prior versus 27,800 × 10⁶ cells/L in samples taken post antimicrobial initiation; p = 0.053). One sample was B. pseudomallei culture-positive 32 days following antimicrobial initiation. The presence/absence of contiguous osteomyelitis did not alter synovial fluid white cell counts. These findings suggest that in cases of suspected melioidosis SA, it is not necessary to withhold empirical antimicrobial therapy while awaiting joint aspiration. Further research is needed to define the role of non-culture-based diagnostics in suspected melioidosis SA. Full article

(This article belongs to the Special Issue Diagnostic Challenges in Joint Infections: From Culture to Molecular Techniques)

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17 pages, 275 KB

Open AccessReview

Ceftazidime/Avibactam Monotherapy Versus Other Antibiotics: Where Do We Stand?

by Georgios Vougiouklakis, Constantinos Tsioutis, Nayia Vasileiadi, Konstantinos Alexakis, Nikolaos Spernovasilis and Aris P. Agouridis

Pathogens 2025, 14(11), 1119; https://doi.org/10.3390/pathogens14111119 - 3 Nov 2025

Abstract

The global rise of multi-drug resistant (MDR) pathogens, including the widespread resistance to beta-lactams through the production of β-lactamases, like extended spectrum β-lactamases (ESBLs), has led to the increasing use of last-line antibiotics such as carbapenems. Subsequently, the worldwide emergence of carbapenemase-producing pathogens [...] Read more.

The global rise of multi-drug resistant (MDR) pathogens, including the widespread resistance to beta-lactams through the production of β-lactamases, like extended spectrum β-lactamases (ESBLs), has led to the increasing use of last-line antibiotics such as carbapenems. Subsequently, the worldwide emergence of carbapenemase-producing pathogens poses a formidable challenge. The combination ceftazidime/avibactam (CAZ/AVI) has emerged as a pivotal agent in the management of multidrug-resistant Gram-negative infections. Avibactam, a novel β-lactamase inhibitor, demonstrates a wider spectrum of activity against Ambler Class A, C, and partially D β-lactamases in comparison to older inhibitors, thus enhancing the antimicrobial activity of ceftazidime against organisms producing ESBL and carbapenemases, such as oxacillinase (OXA)-type and Klebsiella pneumoniae Carbapenemase (KPC). This review synthesizes findings from randomized controlled trials and cohort studies, evaluating the efficacy of CAZ/AVI across diverse clinical settings, including complicated intra-abdominal infections, urinary tract infections, nosocomial pneumonia, skin and soft tissue infections, and bloodstream infections. The non-inferiority of CAZ-AVI with respect to carbapenems and superiority over polymyxins in terms of both clinical outcomes and safety are outlined, along with evidence supporting the use of CAZ/AVI in high-risk populations such as immunocompromised and critically ill patients. Overall, CAZ/AVI represents a compelling therapeutic option with favorable efficacy and safety, thus appearing as a reasonable frontline treatment for resistant Gram-negative infections. Full article

(This article belongs to the Special Issue Advanced Antimicrobial Agents: Combatting Multi-Drug Resistant Bacterial Infections)

4 pages, 627 KB

Open AccessCorrection

Correction: Jamshaid et al. Bone Loss and Fractures in Post-Menopausal Women Living with HIV: A Narrative Review. Pathogens 2024, 13, 811

by Maryam Jamshaid, Amirmohammad Heidari, Ahmed Hassan, Dushyant Mital, Oliver Pearce, Maria Panourgia and Mohamed H. Ahmed

Pathogens 2025, 14(11), 1118; https://doi.org/10.3390/pathogens14111118 - 3 Nov 2025

Abstract

In the original publication [...] Full article

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17 pages, 306 KB

Open AccessReview

Toxocara Seroprevalence in Europe and Considerations for Future Research

by Roxana Gabriela Cobzaru, Carmen Valerica Ripa, Ramona Gabriela Ursu, Miruna Raluca Ripa, Costin Damian and Luminita Smaranda Iancu

Pathogens 2025, 14(11), 1117; https://doi.org/10.3390/pathogens14111117 - 3 Nov 2025

Abstract

Toxocarosis is one of the most widespread zoonotic parasitic diseases, caused by Toxocara canis and Toxocara cati. Studying the epidemiological situation is a real challenge for specialists in the field worldwide. The aim of this study was to highlight the epidemiological aspects [...] Read more.

Toxocarosis is one of the most widespread zoonotic parasitic diseases, caused by Toxocara canis and Toxocara cati. Studying the epidemiological situation is a real challenge for specialists in the field worldwide. The aim of this study was to highlight the epidemiological aspects of the prevalence rate in Europe, and we found that the distribution of Toxocara infection is uneven, depending on geographical, climatic and socio-economic factors. Currently, there is a continuous spread of this parasite in many regions, including economically developed countries, but the exact prevalence is not known because there are no regular reports and statistical evidence regarding toxocarosis. The presence of nonspecific symptoms and subclinical disease may delay diagnosis and treatment, with long-term implications for the patient, and because of this, we discussed the possible Toxocara detection methods, with several novel and interesting approaches. Toxocarosis is included among the neglected parasitic diseases, requiring seroprevalence studies to be carried out to develop programs to reduce the frequency of this parasitosis. Full article

(This article belongs to the Special Issue Parasitic Diseases in the Contemporary World)

13 pages, 1525 KB

Open AccessArticle

Construction of a Risk Assessment Model for Short-Term Mortality in Patients with Invasive Fungal Diseases Post-Cardiac Surgery Based on Multivariate Analysis

by Dong Wei, Qi Shen and Qian Zhai

Pathogens 2025, 14(11), 1116; https://doi.org/10.3390/pathogens14111116 - 3 Nov 2025

Abstract

To develop and validate a predictive model for assessing the risk of short-term mortality in patients with invasive fungal diseases (IFDs) following cardiac surgery. This retrospective study analyzed clinical data from patients diagnosed with postoperative IFDs in the cardiac surgical intensive care unit [...] Read more.

To develop and validate a predictive model for assessing the risk of short-term mortality in patients with invasive fungal diseases (IFDs) following cardiac surgery. This retrospective study analyzed clinical data from patients diagnosed with postoperative IFDs in the cardiac surgical intensive care unit (ICU) of Qilu Hospital of Shandong University (QLH), between January 2020 and December 2023. A total of 98 patients were included and divided into a non-survival group (n = 42) and a survival group (n = 56) based on 28-day mortality. Demographic, clinical, and postoperative parameters were collected. The Least Absolute Shrinkage and Selection Operator (LASSO) regression was used for variable selection, and selected variables were then entered into multivariate logistic regression to identify independent risk factors. A nomogram was developed, and its predictive performance was evaluated using the receiver operating characteristic (ROC) curve, decision curve analysis (DCA), and clinical impact curve (CIC). Multivariate logistic regression, following variable selection by LASSO, identified a history of smoking, an elevated SOFA score, mean arterial pressure (MAP) below 70 mmHg, and tachyarrhythmia as independent risk factors for short-term mortality in this cohort (p < 0.05). The prediction model demonstrated excellent discrimination, with an area under the ROC curve (AUC) of 0.886 (95% CI: 0.816–0.957). The calibration curve showed good agreement between predicted and observed outcomes, with a mean absolute error of 0.023. Decision curve analysis indicated a net clinical benefit across a threshold probability range of 0.1 to 0.87. The clinical impact curve confirmed a high concordance between predicted mortality and actual outcomes. A history of smoking, an elevated SOFA score, MAP below 70 mmHg, and tachyarrhythmia independently predict short-term mortality in patients with IFDs after cardiac surgery. Therefore, the nomogram constructed from these factors provides an accurate and clinically applicable tool for risk stratification. Full article

(This article belongs to the Topic Pathophysiology and Clinical Management of Fungal Infections)

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13 pages, 393 KB

Open AccessArticle

Seroprevalence of Tick-Borne Encephalitis Virus in Latvia Using Standard and Subtype-Specific NS1-Based ELISA Assays

by Zane Freimane, Gerhard Dobler, Guntis Karelis, Lidia Chitimia-Dobler, Oksana Savicka and Dace Zavadska

Pathogens 2025, 14(11), 1115; https://doi.org/10.3390/pathogens14111115 - 2 Nov 2025

Abstract

Background: Latvia is one of the most endemic tick-borne encephalitis (TBE) countries in Europe. However, assessing TBE seroprevalence and true infection rates has been challenging. Current diagnostics cannot reliably distinguish between immune responses induced by natural infection from those induced by vaccination, especially [...] Read more.

Background: Latvia is one of the most endemic tick-borne encephalitis (TBE) countries in Europe. However, assessing TBE seroprevalence and true infection rates has been challenging. Current diagnostics cannot reliably distinguish between immune responses induced by natural infection from those induced by vaccination, especially in TBE endemic countries with recommended immunisation programmes. A recently developed ELISA targeting antibodies against TBEV non-structural protein 1 (NS1) offers improved specificity for natural infection and can differentiate among three clinically relevant TBEV subtypes. Methods: We conducted a cross-sectional TBEV seroprevalence study in the Latvian population during 2019–2022, consisting of two pools: 1020 residents living in different regions of Latvia and 200 random Latvian Biobank blood samples. We used the standard anti-TBEV IgG ELISA (VIDITEST, VIDIA, Czech Republic) for the screening and detection of TBEV (whole virus) IgG antibodies and the newly established research-use anti-TBEV NS1 IgG ELISA for the detection of subtype-specific TBEV NS1 IgG antibodies against three virus subtypes: European, Siberian and Far Eastern. Results: The total TBEV seroprevalence among 1020 residents was 39.7%, representing all age cohorts of the population from all regions of Latvia. In total, 33.4% of the enrolled population were vaccinated against TBE with at least one dose of the TBE vaccine. Among the unvaccinated population, 16.3% had positive TBEV-specific IgG antibodies by standard ELISA. On the contrary, NS1-specific antibodies, indicating past natural infection, were detected in only 4.3% of the overall study population. Subtype differentiation revealed infections from all three major TBEV subtypes present in Latvia. Conclusions: In conclusion, this population-based study highlights a high risk of TBE in Latvia, with substantial seroprevalence even among unvaccinated individuals. The NS1-based ELISA enhances the accuracy of TBE surveillance and offers important clinical utility by facilitating more reliable diagnosis and case classification, regardless of vaccination status. Full article

(This article belongs to the Special Issue Tick-Borne Threats in Europe: From Epidemiology to the Impact of Vaccination)

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12 pages, 2066 KB

Open AccessArticle

Burden of Soil-Transmitted Helminth Infections in China: Historical Trends (1990–2021) and Future Projections (2035)

by Bixian Ni, Yanzheng Zou, Luqiu Tao and Wei Wang

Pathogens 2025, 14(11), 1114; https://doi.org/10.3390/pathogens14111114 - 2 Nov 2025

Abstract

Background: Soil-transmitted helminth (STH) infections, including ascariasis, trichuriasis, and hookworm disease, are among the most common neglected tropical diseases (NTDs) globally. This study evaluates the disease burden of STH in China from 1990 to 2021 and projects trends to 2035. Methods: Data from [...] Read more.

Background: Soil-transmitted helminth (STH) infections, including ascariasis, trichuriasis, and hookworm disease, are among the most common neglected tropical diseases (NTDs) globally. This study evaluates the disease burden of STH in China from 1990 to 2021 and projects trends to 2035. Methods: Data from the Global Burden of Disease 2021 database were utilized to analyze the prevalence and disability-adjusted life years (DALYs) of STH infections in China from 1990 to 2021. The estimated annual percentage change (EAPC) was calculated to assess trends over time, and a Bayesian age-period-cohort model was used to project the disease burden up to 2035. Results: From 1990 to 2021, the prevalence and DALYs of STH infections decreased significantly by 85.08% and 98.01% in China, respectively. The age-standardized prevalence rate (ASPR) of STH infections dropped from 34,073.24/10⁵ to 4981.01/10⁵ with an EAPC of −6.62% [95% confidence interval (CI): −7.40%, −5.83%], and the age-standardized DALY rate (ASDR) decreased from 1.77/10⁵ to 0.18/10⁵, with an EAPC of −14.05% (95% CI: −15.04%, −13.06%). Trichuriasis contributed to 78.85% of the total ASPR for STH, whereas hookworm disease accounted for 51.14% of STH’s ASDR. The highest disease burden due to STH peaked in the 5–9 years age group, with prevalence of 8030.05/10⁵ [95% uncertainty interval (UI): 5356.86/10⁵–11,662.62/10⁵] and DALYs rate of 2.99/10⁵ (95% UI: 1.56/10⁵−4.87/10⁵). The projected ASDR and ASPR of trichuriasis rose to 0.55/10⁵ and 5362.50/10⁵ by 2035. Conclusions: China has achieved remarkable reductions in the burden of STH infections over the past three decades. However, the predominance between the species has changed. The projected rebound in trichuriasis underscores the importance of sustained control efforts. To achieve the 2030 elimination target outlined in the WHO NTDs roadmap, it is crucial to integrate precision epidemiology with ongoing water, sanitation, and hygiene initiatives, targeted chemotherapy and health education. Full article

(This article belongs to the Special Issue New Advances in Epidemiology of Neglected Tropical Diseases)

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30 pages, 7381 KB

Open AccessArticle

Challenges and Opportunities of Bacterial Vaccines as Alternatives to Antimicrobials in Swine Health Management: Insights from U.S. Veterinarians

by Xirui Zhang, Danqin Li, Michael D. Apley, Locke Karriker, Joseph F. Connor, Corinne Bromfield, Jordan T. Gebhardt, Brian Lubbers, Hatem Kittana, Dustin Pendell, Rachel Madera, Nina Muro, Aidan Craig, Brooke Shenkenberg, Yuzhen Li, Lihua Wang and Jishu Shi

Pathogens 2025, 14(11), 1113; https://doi.org/10.3390/pathogens14111113 - 1 Nov 2025

Abstract

Antimicrobial resistance (AMR) is a significant global health concern, and the use of antibiotics in livestock, including swine production, is a major contributor. Vaccines offer a promising alternative for controlling bacterial infections in pigs, but their widespread use is often hindered by biological, [...] Read more.

Antimicrobial resistance (AMR) is a significant global health concern, and the use of antibiotics in livestock, including swine production, is a major contributor. Vaccines offer a promising alternative for controlling bacterial infections in pigs, but their widespread use is often hindered by biological, economic, and practical challenges. This study surveyed U.S. swine veterinarians to identify which bacterial diseases require better vaccines and to understand the barriers to their adoption. Nineteen veterinarians with an average of 24.7 years of experience were surveyed across 21 states. The results identified Streptococcus suis, Escherichia coli, Mycoplasma hyopneumoniae, and Glaesserella parasuis as the most critical pathogens needing improved vaccines. Veterinarians anticipated significant improvements in vaccine efficacy for S. suis and E. coli during the nursery stage and expressed a willingness to pay 1.8 and 1.9 times their current prices, respectively. While expectations for M. hyo vaccine improvements were not significant, veterinarians expressed the highest willingness to pay (4.2 times the current price), citing the potential for disease eradication. This research highlights that developing effective vaccines for S. suis and E. coli should be the most urgent priority due to their significant economic impact and rising AMR concerns. However, M. hyo vaccine development holds the most economic potential due to the possibility of eradication. Our research provides a roadmap for future efforts to combat AMR in the swine industry, emphasizing key economic, policy, and educational considerations for successful vaccine implementation. Full article

(This article belongs to the Special Issue Advancing Vaccine Strategies and Technologies for Controlling Swine Infectious Diseases)

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16 pages, 413 KB

Open AccessArticle

Comparative Efficacy of a Novel Topical Formulation with Antimicrobial Peptides and Encapsulated Plant Extracts Versus Conventional Therapies for Canine Otitis Externa

by Tatiana Charello Bannach, Anna Claudia Baumel Mongruel, Alberto Gonçalves Evangelista, Vitória Brigida Mielnik de Souza, Renata Voi, Michel Fleith Otuki, Marconi Rodrigues de Farias and Fernando Bittencourt Luciano

Pathogens 2025, 14(11), 1112; https://doi.org/10.3390/pathogens14111112 - 1 Nov 2025

Abstract

Canine otitis externa (OE) presents a significant challenge in veterinary medicine due to its complex, multifactorial nature and the growing issue of antimicrobial resistance (AMR) associated with conventional antibiotic use. The objective of this study was to compare the efficacy of a novel, [...] Read more.

Canine otitis externa (OE) presents a significant challenge in veterinary medicine due to its complex, multifactorial nature and the growing issue of antimicrobial resistance (AMR) associated with conventional antibiotic use. The objective of this study was to compare the efficacy of a novel, antibiotic-free topical ear solution (Therapy A) containing antimicrobial peptides and encapsulated plant extracts (chamomile, calendula, rosemary, and hops) against a standard conventional treatment (Therapy B) composed of gentamicin, betamethasone valerate, and clotrimazole. A longitudinal, randomized study was conducted over four weeks with 40 domestic dogs diagnosed with OE. The dogs were divided into two groups, each receiving one of the therapies. Evaluations were performed weekly, assessing clinical signs using the Otitis Index Scoring System (OTIS-3) and a pruritus visual analog scale (pVAS), as well as ear canal pH and cytology. The results showed that Therapy A provided similar clinical efficacy in OTIS-3 and pVAS scores that were comparable to Therapy B. Cytological analysis also revealed a significant reduction in microbial presence for both groups. Notably, Therapy A was clinically effective in two of the three dogs presenting multi-drug resistant (MDR) bacterial infections. The novel formulation also demonstrated a favorable safety profile, with no adverse drug reactions reported, in contrast to one dog in the conventional treatment group that experienced an adverse reaction. These findings suggest that the plant-based formulation is a safe and effective alternative for managing canine OE, offering a promising solution to reduce the reliance on antibiotics and corticosteroids. Full article

(This article belongs to the Special Issue Diagnostic and Therapeutic Approach of Otitis Externa and Media in Dogs and Cats)

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28 pages, 2097 KB

Open AccessReview

The Human Archaeome: Commensals, Opportunists, or Emerging Pathogens?

by Douglas M. Ruden

Pathogens 2025, 14(11), 1111; https://doi.org/10.3390/pathogens14111111 - 31 Oct 2025

Abstract

Archaea, one of the three domains of life, are increasingly recognized as consistent, though often underappreciated, members of the human microbiome, yet their roles in health and disease remain poorly understood. Unlike bacteria, no archaeal species have been conclusively identified as primary mammalian [...] Read more.

Archaea, one of the three domains of life, are increasingly recognized as consistent, though often underappreciated, members of the human microbiome, yet their roles in health and disease remain poorly understood. Unlike bacteria, no archaeal species have been conclusively identified as primary mammalian pathogens, but their widespread presence across diverse body sites suggests potential indirect contributions to host physiology and pathology. Current evidence is synthesized on archaeal diversity and habitat specificity across multiple human-associated sites, encompassing the gastrointestinal, aerodigestive, and urogenital tracts as well as the skin. Methanogens dominate the lower gastrointestinal tract (LGT), where they influence fermentation dynamics and methane production, while members of the class Nitrososphaeria are prevalent on the skin and upper aerodigestive tract (UAT), reflecting ecological specialization. Variability in archaeal composition across niches highlights possible links to disease processes: methanogens have been associated with irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), obesity, and colorectal cancer (CRC); Methanobrevibacter oralis is enriched in periodontal disease; and archaea have been detected in the lungs of cystic fibrosis patients. Although archaea lack canonical bacterial virulence factors, they may contribute indirectly through metabolic cross-feeding, immune modulation, synergy in polymicrobial infections, and alteration of host–microbiome network dynamics. This review explores the emerging concept of the human “archaeome”, evaluates current evidence for archaeal involvement in disease, and highlights emerging technologies, such as bacteria-MERFISH and multi-omics profiling, that enable translational applications including microbiome diagnostics, therapeutic targeting, and microbiome engineering. Full article

(This article belongs to the Special Issue Diagnosis, Immunopathogenesis and Control of Bacterial Infections)

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13 pages, 1494 KB

Open AccessArticle

Clinical Characteristics of Adenovirus Pneumonia in Children

by Huifen Xu, Wei Chen, Qinrui Lai, Yingying Chen, Yajun Guo, Jing Chen and Wei Li

Pathogens 2025, 14(11), 1110; https://doi.org/10.3390/pathogens14111110 - 31 Oct 2025

Abstract

Identifying effective indicators and developing predictive models for the early detection of severe adenoviral pneumonia (SAP) is critical to safeguarding patients’ lives. This study examined differences between 428 patients with SAP and those with non-severe adenoviral pneumonia (NSAP) from March 2022 to January [...] Read more.

Identifying effective indicators and developing predictive models for the early detection of severe adenoviral pneumonia (SAP) is critical to safeguarding patients’ lives. This study examined differences between 428 patients with SAP and those with non-severe adenoviral pneumonia (NSAP) from March 2022 to January 2023, focusing on variables such as age, sex, type of coinfection, and a range of clinical laboratory indicators. SAP was significantly more common in children aged 3–6 years (20/54 of all SAP cases, p = 0.0258) and among those with polymicrobial coinfections (p < 1.20 × 10⁻¹¹). Patients with SAP exhibited significantly higher prealbumin (PA) level, while C-reactive protein (CRP) level was significantly lower. Composite indicator, such as CRP -to- prealbumin ratio (CPAR), was also significantly elevated (p < 0.05). The random forest model achieved an area under the receiver operating characteristic (ROC) curve (AUC) of 0.699, with an accuracy of 84.5% and a precision of 91.5%. Analysis of the data revealed key predictive parameters for early-stage SAP. Indicators such as CPAR, PA, and CRP are valuable for assessing SAP risk. Moreover, commonly available clinical indicators can effectively construct a random forest-based predictive model for SAP. Full article

(This article belongs to the Section Viral Pathogens)

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11 pages, 222 KB

Open AccessArticle

Dalbavancin for Bone and Joint Infections: A Two-Center Greek Real-World Retrospective Study

by Christina Petropoulou, Petros Ioannou, Georgios Eleftherakis, Stefania Papazisi, Christos Davoulos, Eugenia Drosou, Anastasia Spiliopoulou, Ekaterini Tsiata, Fotini Paliogianni, Diamantis Kofteridis, Markos Marangos and Stelios F. Assimakopoulos

Pathogens 2025, 14(11), 1109; https://doi.org/10.3390/pathogens14111109 - 31 Oct 2025

Abstract

Bone and joint infections remain therapeutic challenges, usually requiring prolonged intravenous therapy and hospitalization. Dalbavancin, a long-acting lipoglycopeptide, offers a simplified alternative. We retrospectively analysed 83 patients treated with dalbavancin for osteomyelitis, spondylodiscitis, septic arthritis, or prosthetic joint infection in two tertiary Greek [...] Read more.

Bone and joint infections remain therapeutic challenges, usually requiring prolonged intravenous therapy and hospitalization. Dalbavancin, a long-acting lipoglycopeptide, offers a simplified alternative. We retrospectively analysed 83 patients treated with dalbavancin for osteomyelitis, spondylodiscitis, septic arthritis, or prosthetic joint infection in two tertiary Greek hospitals (2022–2024). Mean age was 69 ± 16 years; 56.6% were male; Charlson Comorbidity Index averaged 4 ± 2.25. Common comorbidities included diabetes (28.9%) and coronary artery disease (18.1%). Infections were vertebral osteomyelitis/spondylodiscitis (48.2%), non-vertebral osteomyelitis (38.5%), prosthetic joint infection (10.8%), and septic arthritis (8.4%). Microbiological diagnosis was established in 62.6%; predominant pathogens were Staphylococcus aureus (38.4%: 30.7% MSSA, 7.7% MRSA) and enterococci (25%, including 5.7% VRE). Dalbavancin was administered as monotherapy (32.4%) or combined with other antibiotics (67.6%), mainly fluoroquinolones (63.6%) and minocycline (23.6%). Mean dosing was 2 ± 2.36 administrations (4 ± 4.38 g total). Surgical debridement was performed in 36.1% of patients. Clinically significant adverse events occurred in 4 patients (4.8%): acute kidney injury (n = 2), angioedema (n = 1), and Clostridioides difficile colitis (n = 1). Clinical cure was achieved in 90.4% at day 90 and 92.8% at day 180. Clinical cure rates were comparable between dalbavancin monotherapy and combination therapy, suggesting that the efficacy observed was primarily attributable to dalbavancin itself. Relapse at one year occurred in 10.8%, mainly due to inadequate source control. Dalbavancin demonstrated high efficacy, favourable safety, and treatment simplification in complex bone and joint infections. Its long half-life and reduced need for prolonged IV access support its role in minimizing hospitalization and catheter-related complications, particularly in regions with limited outpatient parenteral therapy infrastructure. Full article

(This article belongs to the Special Issue Infections and Bone Damage)

23 pages, 2087 KB

Open AccessArticle

Whole Genome Sequencing and Comparative Genomics of the Emerging Pathogen Burkholderia pseudomallei Isolated from Two Travel-Related Infections in Hungary

by Judit Henczkó, Ákos Tóth, Márta Knausz, Béla Gartner, Ákos Reményi, Edit Bíró, Erzsébet Létay, László Rókusz, Szilárd Tóth, Bernadett Pályi, Tünde Mag, Tímea Erdősi, Nóra Deézsi-Magyar, Zsuzsanna Molnár and Zoltán Kis

Pathogens 2025, 14(11), 1108; https://doi.org/10.3390/pathogens14111108 - 31 Oct 2025

Abstract

Background: Burkholderia pseudomallei, the causative agent of melioidosis, is a neglected tropical pathogen that has been increasingly encountered in Europe through travel-related infections. Clinical manifestations range from localized abscesses to life-threatening sepsis, posing diagnostic challenges in non-endemic regions. Methods: We report two [...] Read more.

Background: Burkholderia pseudomallei, the causative agent of melioidosis, is a neglected tropical pathogen that has been increasingly encountered in Europe through travel-related infections. Clinical manifestations range from localized abscesses to life-threatening sepsis, posing diagnostic challenges in non-endemic regions. Methods: We report two travel-associated melioidosis cases confirmed in Hungary between 2008 and 2024. Whole-genome sequencing (WGS), multilocus sequence typing (MLST), and core-genome MLST (cgMLST) were performed for molecular characterization. In parallel, a systematic review of travel-related melioidosis cases reported in Europe (1980–2025) was conducted according to PRISMA 2020 guidelines. Data were retrieved from PubMed, Scopus, Google Scholar, and the PubMLST database. Results: In silico MLST identified two distinct sequence types (STs): a novel ST1643, and ST1051, previously reported in Asia and Australia. Both isolates clustered within the Asian clade, confirming an imported origin. Virulence profiling revealed major determinants, including the Yersinia-like fimbriae (YLF) cluster, fhaB3, and ITS type C. The ST1643 isolate carried the bimA_Bm variant and multiple resistance genes (blaOXA-57, blaPenI, and amrAB efflux system), while ST1051 harbored blaOXA-59. The literature review identified 82 studies encompassing 195 European cases, most originating from Southeast Asia, with pneumonia, followed by septic form and abscess as the predominant presentation. We found only eight neuromelioidosis cases in Europe. Conclusions: This study represents the first report of neuromelioidosis in Hungary, and the first global description of ST1643. Combined genomic and epidemiological data highlight the need for improved clinical awareness, genomic surveillance, and diagnostic preparedness in non-endemic regions, as global travel and climate change expand the distribution of melioidosis. Full article

(This article belongs to the Special Issue Updates on Human Melioidosis)

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12 pages, 1060 KB

Open AccessArticle

Epidemiological Characteristics of HSV-1 and HSV-2 in 177,599 Patients Based on PCR Testing in South Korea (2018–2022)

by Hyeong Ho Kim, Sung Hun Jang, Jeong Su Han, Jae-Sik Jeon and Jae Kyung Kim

Pathogens 2025, 14(11), 1107; https://doi.org/10.3390/pathogens14111107 - 30 Oct 2025

Abstract

HSV-1 is associated with oral lesions and non-sexual transmission; HSV-2 is primarily transmitted through sexual contact and causes genital infections. Understanding the epidemiological dynamics of both viruses is essential for guiding targeted public-health responses. We conducted a retrospective analysis of 177,599 clinical specimens [...] Read more.

HSV-1 is associated with oral lesions and non-sexual transmission; HSV-2 is primarily transmitted through sexual contact and causes genital infections. Understanding the epidemiological dynamics of both viruses is essential for guiding targeted public-health responses. We conducted a retrospective analysis of 177,599 clinical specimens collected between September 2018 and December 2022 from patients with symptoms suggestive of sexually transmitted infections (STIs) at healthcare institutions across South Korea. HSV-1 and HSV-2 were identified using a real-time PCR assay; positivity rates were stratified by age, sex, specimen type, and year of testing. The overall positivity rate was 0.26% for HSV-1 and 1.60% for HSV-2. HSV-1 was most prevalent among individuals aged <19 years; HSV-2 showed the highest positivity in females aged 20–29 years, declining with age thereafter. HSV-2 positivity was significantly higher in females than in males. A significant decline in HSV-2 positivity was observed over the 5-year study period, while HSV-1 positivity remained stable. This nationwide PCR-based study reveals distinct age- and sex-related epidemiological patterns of HSV-1 and HSV-2. The findings support the need for age-specific and gender-specific STI screening strategies and health education programs. The declining trend in HSV-2 infection may reflect the impact of recent public-health initiatives. Full article

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13 pages, 3018 KB

Open AccessArticle

Development of Immunodetection Systems Using a Specific Antibody Against the Recombinant Coat Protein for Detecting Sugarcane Streak Mosaic Virus

by Intan Ria Neliana, Bambang Sugiharto, Rikno Harmoko and Wahyu Indra Duwi Fanata

Pathogens 2025, 14(11), 1106; https://doi.org/10.3390/pathogens14111106 - 30 Oct 2025

Abstract

Sugarcane streak mosaic virus (SCSMV) is one of the mosaic viruses found in mixed infection with two or more viruses. Infections of mosaic viruses show highly similar mosaic symptoms and are difficult to distinguish. This study aimed to develop a specific antibody against [...] Read more.

Sugarcane streak mosaic virus (SCSMV) is one of the mosaic viruses found in mixed infection with two or more viruses. Infections of mosaic viruses show highly similar mosaic symptoms and are difficult to distinguish. This study aimed to develop a specific antibody against SCSMV that could potentially be utilized to differentiate mosaic virus infections. The cDNA encoding the coat protein (CP) of SCSMV was isolated by RT-PCR from the symptomatic sugarcane leaves. The cDNA was then used for the production of CP for the development of its polyclonal antibody. The nucleotide sequence of the cDNA showed high homology of 94.2–97.3% at the amino acid level with the CP-cDNA of SCSMV isolated from India (AM749403.1), Africa (OR195142.1), and USA (U75456.1). CP was produced as a recombinant protein with a molecular size of 36.5 kDa in Escherichia coli. The injection of recombinant CP into a rabbit resulted in the production of polyclonal antibodies, which were used for the immunodetection of SCSMV in sugarcane. Immunoblot analysis revealed a specific reaction of SCSMV-CP in symptomatic sugarcane leaves. ELISA (Enzyme-Linked Immunosorbent Assay) and IC-RT-PCR (Immunocapture-Reverse Transcription-Polymerase Chain Reaction) using the CP antibody proved successful for detecting SCSMV infection in sugarcane leaves. The results indicate that the SCSMV-CP antibody is suitable for an immunodetection system and exhibits high specificity for SCSMV infection. Full article

(This article belongs to the Section Viral Pathogens)

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15 pages, 7711 KB

Open AccessArticle

Trem2-MICAL1-P-ERK Axis in Macrophages Confers Protection Against Toxoplasma gondii-Induced Adverse Pregnancy Outcomes

by Xiaoyu Geng, Haochen Yang, Zihan Wang, Ziqian Chen, Jinling Chen and Mei Yang

Pathogens 2025, 14(11), 1105; https://doi.org/10.3390/pathogens14111105 - 30 Oct 2025

Abstract

Toxoplasma gondii (T. gondii) infection during pregnancy can cause severe placental damage and fetal impairment. Although triggering the receptor expressed on myeloid cells 2 (Trem2) confers protection against T. gondii infection, the precise molecular mechanisms underlying this immunoregulatory role remain incompletely understood. [...] Read more.

Toxoplasma gondii (T. gondii) infection during pregnancy can cause severe placental damage and fetal impairment. Although triggering the receptor expressed on myeloid cells 2 (Trem2) confers protection against T. gondii infection, the precise molecular mechanisms underlying this immunoregulatory role remain incompletely understood. Using a mouse model, this study identifies a novel Trem2-MICAL1-P-ERK axis in macrophages that protects against T. gondii-induced adverse pregnancy outcomes (APO). RNA-seq of Trem2-overexpressing macrophages revealed significant upregulation of 1857 genes, with MICAL1 among the most markedly altered, highlighting its potential role in Trem2-mediated signaling. Mechanistically, correlation analysis, molecular docking, fluorescence co-localization, and immunoprecipitation assays demonstrate that Trem2 directly interacts with MICAL1, which modulates downstream phosphorylated ERK (P-ERK) signaling. In a T. gondii-infected murine pregnancy model, genetic ablation of Trem2 exacerbated pathogen-induced suppression of MICAL1 and P-ERK, whereas macrophage-specific overexpression of Trem2-DAP12 restored this signaling axis. Conversely, MICAL1 overexpression rescued P-ERK activation but failed to regulate Trem2 expression. Further studies in bone marrow-derived macrophages (BMDMs) revealed that Trem2 deficiency potentiated the inhibitory effects of soluble T. gondii antigens (TgAg) on MICAL1 and P-ERK. These findings elucidate how T. gondii disrupts placental immunity through targeted suppression of Trem2-mediated signaling and establish the Trem2-MICAL1-P-ERK cascade as a core regulatory pathway in immune homeostasis during pregnancy. Full article

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