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Assessing the Prevalence and Dynamics of Emerging Campylobacterales in Human Stool Samples in Brussels by Filtration Culture
Zika Virus Neuropathogenesis
Co-Infections and Superinfections between HIV-1 and Other Human Viruses at the Cellular Level

Journal Description

Pathogens

Pathogens is an international, peer-reviewed, open access journal on pathogens and pathogen-host interactions published monthly online by MDPI.

Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, Embase, PubAg, CaPlus / SciFinder, AGRIS, and other databases.
Journal Rank: JCR - Q2 (Microbiology) / CiteScore - Q2 (General Immunology and Microbiology )
Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 16.3 days after submission; acceptance to publication is undertaken in 2.6 days (median values for papers published in this journal in the first half of 2024).
Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
Companion journals for Pathogens include: Parasitologia, Bacteria and Zoonotic Diseases.

Impact Factor: 3.3 (2023); 5-Year Impact Factor: 3.5 (2023)

Imprint Information Journal Flyer Open Access ISSN: 2076-0817

Latest Articles

14 pages, 461 KiB

Open AccessReview

HPV and Penile Cancer: Epidemiology, Risk Factors, and Clinical Insights

by Gowtam Mannam, Justin W. Miller, Jeffrey S. Johnson, Keerthi Gullapalli, Adnan Fazili, Philippe E. Spiess and Jad Chahoud

Pathogens 2024, 13(9), 809; https://doi.org/10.3390/pathogens13090809 (registering DOI) - 18 Sep 2024

Penile cancer (PC) is a rare malignancy predominantly of squamous cell origin. Approximately 40% of penile tumors are associated with human papillomavirus (HPV) infection. Diagnosing PC remains challenging due to its rarity and variety of clinical presentations. Furthermore, the impact of HPV on [...] Read more.

Penile cancer (PC) is a rare malignancy predominantly of squamous cell origin. Approximately 40% of penile tumors are associated with human papillomavirus (HPV) infection. Diagnosing PC remains challenging due to its rarity and variety of clinical presentations. Furthermore, the impact of HPV on the tumor immune microenvironment complicates clinical management, although recent advancements in immune checkpoint inhibitors (ICIs) have shown some efficacy in treating HPV-associated PC. Ongoing research efforts aim to develop oncologic treatments that target HPV-induced cellular modifications. Additionally, novel therapeutic vaccines and adoptive T-cell therapies targeting HPV oncoproteins represent emerging treatment modalities. Our review highlights the complex interplay between HPV and penile carcinogenesis, emphasizing its epidemiology, etiology, clinicopathological characteristics, and potential therapeutic implications. Full article

(This article belongs to the Special Issue Oncogenic Viruses: Advances in Molecular Diagnosis, Prevention Strategies and Therapy)

12 pages, 1382 KiB

Open AccessArticle

The Negative Impact of Maternal HIV Infection on Birth Outcomes—Myth or Reality?

by Tudor Fleșeriu, Lorena Elena Meliț, Cristina Oana Mărginean and Anca-Meda Văsieșiu

Pathogens 2024, 13(9), 808; https://doi.org/10.3390/pathogens13090808 (registering DOI) - 18 Sep 2024

Human Immunodeficiency Virus (HIV) infection during pregnancy poses significant risks to both maternal and child health, with potential adverse effects on perinatal outcomes. This study aimed to compare perinatal outcomes, including birth weight, length, Apgar scores, and prematurity rates, between HIV-exposed, uninfected (HEU) [...] Read more.

Human Immunodeficiency Virus (HIV) infection during pregnancy poses significant risks to both maternal and child health, with potential adverse effects on perinatal outcomes. This study aimed to compare perinatal outcomes, including birth weight, length, Apgar scores, and prematurity rates, between HIV-exposed, uninfected (HEU) children and HIV-unexposed, uninfected (HUU) children. A total of 204 neonates were included in the study, comprising 102 born to HIV-positive mothers and 102 born to uninfected mothers. Our findings revealed significant differences in birth weight (p < 0.001), length (p < 0.001), and Apgar scores at both 1 min (p = 0.003) and 5 min (p < 0.001) between HIV-exposed and -unexposed children. The HIV-exposed group exhibited lower birth weights and lengths, along with lower Apgar scores, indicating potential neonatal health challenges. No significant disparities were observed in the prematurity risk between the two groups (OR = 2.58, p = 0.126), but the risk of being born small for gestational age (SGA) in the case of HEU newborns was significantly high (OR = 17.41, p < 0.001). The significant differences in birth weight, length, and Apgar scores underscore the need for tailored healthcare interventions and support for neonates born to HIV-positive mothers. These findings contribute to our understanding of the complex interplay between maternal HIV infection and perinatal outcomes, guiding healthcare professionals in delivering targeted care for this vulnerable population. Full article

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16 pages, 483 KiB

Open AccessArticle

Group B Streptococcus Infections in Non-Pregnant Adults, Italy, 2015–2019

by Monica Imperi, Giovanni Gherardi, Giovanna Alfarone and Roberta Creti

Pathogens 2024, 13(9), 807; https://doi.org/10.3390/pathogens13090807 (registering DOI) - 18 Sep 2024

Group B Streptococcus (GBS, Streptococcus agalactiae) is a pathogen of increasing importance in adults. Severe and invasive cases in non-pregnant adults were collected during the period 2015–2019 by voluntary-based surveillance. In total, 108 GBS strains were phenotypically and genotypically characterized for the [...] Read more.

Group B Streptococcus (GBS, Streptococcus agalactiae) is a pathogen of increasing importance in adults. Severe and invasive cases in non-pregnant adults were collected during the period 2015–2019 by voluntary-based surveillance. In total, 108 GBS strains were phenotypically and genotypically characterized for the serotype, antimicrobial resistance, pili, surface protein genes, and the hyper-virulent adhesin hvgA. Patients were divided into two age groups: adults (18–64 years; n = 32) and older adults (≥65 years; n = 72). The average age was 70.8 years, with a male/female ratio of 1.7. Most isolates were recovered from cases of bacteremia (blood, n = 93), and a higher frequency of invasive GBS infections (iGBS) was found among older adults (66.7%). Serotype III was the most frequent (n = 41, 38%), followed by type Ia and type V (n = 20 each, 18.5%). Serotypes Ia, Ib, II, III, IV, and V accounted for all but one isolates (99.1%). The iGBS isolates were universally susceptible to penicillin, while the prevalence of resistance to clindamycin, erythromycin, tetracycline, and high-level gentamicin resistance was 26.8%, 24.1%, 85.2%, and 5.5%, respectively, with the predominance of the erm(B) gene for macrolide resistance and the tet(M) gene for tetracycline resistance. The associations between the serotypes/antimicrobial resistance/virulence traits underlined the increasing importance of serotype III and its contribution to antimicrobial resistance as well as the steady increase over time of serotype IV. This nationwide study confirmed the need for monitoring the GBS epidemiology in non-pregnant adults through continuous surveillance of GBS infections. Full article

13 pages, 2159 KiB

Open AccessArticle

Parasites Diversity, Abundance, Prevalence, and Richness Infecting Didelphis aurita (Didelphimorphia: Didelphidae) in the Atlantic Rainforest, Brazil

by Carolina Romeiro Fernandes Chagas, Cauê Monticelli, Caio Filipe da Motta Lima and Patrícia Locosque Ramos

Pathogens 2024, 13(9), 806; https://doi.org/10.3390/pathogens13090806 - 18 Sep 2024

Parasites are key players in ecosystems, influencing population sizes and food webs, yet the impact of environmental factors on their diversity is not well understood. The Atlantic rainforest in Brazil, particularly the Parque Estadual das Fontes do Ipiranga (PEFI), exemplifies a biodiversity hotspot [...] Read more.

Parasites are key players in ecosystems, influencing population sizes and food webs, yet the impact of environmental factors on their diversity is not well understood. The Atlantic rainforest in Brazil, particularly the Parque Estadual das Fontes do Ipiranga (PEFI), exemplifies a biodiversity hotspot facing significant deforestation, housing diverse animal species such as the synanthropic Brazilian common opossum (Didelphis aurita), which serves as a reservoir for multiple zoonotic pathogens. In this study, we investigated parasite diversity, abundance, prevalence, and richness in free-living D. aurita in the PEFI, São Paulo, Brazil. From January 2015 to January 2017, 101 fecal samples of D. aurita were collected in two areas of PEFI, at the Instituto de Pesquisas Ambientais (IPA) and the Parque de Ciência e Tecnologia (Cientec), and analyzed using three different parasitological methods. In total, 99% of the samples were positive for at least one parasite. The most prevalent parasite belonged to the order Strongylida (82%), followed by Cruzia sp. (77%), the latter having a significantly higher prevalence at IPA. In contrast, Acanthocephala showed greater prevalence at Cientec. Co-infections were common, with some individuals harboring up to seven different parasites. Our findings reveal significant parasite diversity in the D. aurita population at PEFI, including both helminths and protozoan trophozoites, some of which are reported for the first time in this host species. Further research is essential for accurate species identification of the observed parasites. Full article

(This article belongs to the Special Issue Exploring the Biodiversity of Parasites in Humans, Wild and Domestic Animals)

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8 pages, 417 KiB

Open AccessCase Report

First Case Report of Mycotic Abdominal Aortic Aneurysm Caused by Campylobacter fetus in Serbia

by Deana Medic, Milica Devrnja, Nikola Batinic, Djordje Milosevic, Aleksandra Colovic Popadic and Vera Gusman

Pathogens 2024, 13(9), 805; https://doi.org/10.3390/pathogens13090805 - 17 Sep 2024

Background: Due to its distinct vascular tropism, Campylobacter fetus is recognized as a significant cause of severe systemic infections, especially in immunocompromised individuals, while it is rarely reported as a cause of gastrointestinal infections. Methods: A rare case of mycotic abdominal aortic aneurysm [...] Read more.

Background: Due to its distinct vascular tropism, Campylobacter fetus is recognized as a significant cause of severe systemic infections, especially in immunocompromised individuals, while it is rarely reported as a cause of gastrointestinal infections. Methods: A rare case of mycotic abdominal aortic aneurysm associated with Campylobacter fetus detected on the aneurysm wall itself was described. Results: A 68-year-old male was admitted to the hospital due to severe abdominal pain. The patient was afebrile, hemodynamically stable with elevated C-reactive protein levels. A physical examination revealed a palpable, pulsatile, tender mass located in the periumbilical region. Ultrasonography and multi-slice computer tomography angiography (MSCTA) identified an infrarenal abdominal aortic aneurysm with a maximum diameter of 6.5 cm, showing suspicious signs of dissection. Aneurysmectomy with Dacron tube graft interposition was performed. Although the blood cultures remained negative, the culture of the aneurysmal wall grew Campylobacter fetus, enabling early diagnosis and targeted antibiotic therapy. The patient was treated with meropenem for two weeks, followed by amoxicillin-clavulanate for another two weeks after hospital discharge. Conclusions: Campylobacter fetus associated with abdominal aortic aneurysms represents a life-threatening condition, posing a significant challenge in vascular surgery. Due to the lack of clear guidelines on antibiotic susceptibility testing and the treatment of infections associated with this pathogen, enhanced surveillance of Campylobacter fetus is necessary in both human and veterinary medicine. Full article

(This article belongs to the Section Bacterial Pathogens)

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19 pages, 1519 KiB

Open AccessArticle

Increasing Population Immunity Prior to Globally-Coordinated Cessation of Bivalent Oral Poliovirus Vaccine (bOPV)

by Nima D. Badizadegan, Steven G. F. Wassilak, Concepción F. Estívariz, Eric Wiesen, Cara C. Burns, Omotayo Bolu and Kimberly M. Thompson

Pathogens 2024, 13(9), 804; https://doi.org/10.3390/pathogens13090804 - 17 Sep 2024

In 2022, global poliovirus modeling suggested that coordinated cessation of bivalent oral poliovirus vaccine (bOPV, containing Sabin-strain types 1 and 3) in 2027 would likely increase the risks of outbreaks and expected paralytic cases caused by circulating vaccine-derived polioviruses (cVDPVs), particularly type 1. [...] Read more.

In 2022, global poliovirus modeling suggested that coordinated cessation of bivalent oral poliovirus vaccine (bOPV, containing Sabin-strain types 1 and 3) in 2027 would likely increase the risks of outbreaks and expected paralytic cases caused by circulating vaccine-derived polioviruses (cVDPVs), particularly type 1. The analysis did not include the implementation of planned, preventive supplemental immunization activities (pSIAs) with bOPV to achieve and maintain higher population immunity for types 1 and 3 prior to bOPV cessation. We reviewed prior published OPV cessation modeling studies to support bOPV cessation planning. We applied an integrated global poliovirus transmission and OPV evolution model after updating assumptions to reflect the epidemiology, immunization, and polio eradication plans through the end of 2023. We explored the effects of bOPV cessation in 2027 with and without additional bOPV pSIAs prior to 2027. Increasing population immunity for types 1 and 3 with bOPV pSIAs (i.e., intensification) could substantially reduce the expected global risks of experiencing cVDPV outbreaks and the number of expected polio cases both before and after bOPV cessation. We identified the need for substantial increases in overall bOPV coverage prior to bOPV cessation to achieve a high probability of successful bOPV cessation. Full article

(This article belongs to the Special Issue Human Poliovirus)

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16 pages, 7214 KiB

Open AccessArticle

Molecular Confirmation, Epidemiology, and Pathophysiology of Ehrlichia canis Prevalence in Eastern India

by Ankita Chakraborty, Prasana Kumar Rath, Susen Kumar Panda, Bidyut Prava Mishra, Manaswini Dehuri, Sangram Biswal, Manoj Kumar Jena, Basanta Pravas Sahu, Biswaranjan Paital and Dipak Kumar Sahoo

Pathogens 2024, 13(9), 803; https://doi.org/10.3390/pathogens13090803 - 16 Sep 2024

The present study aimed to investigate pathological epidemiology and molecular confirmation of Ehrlichia canis among pet dogs in Bhubaneswar, Odisha, a state in eastern India. A total of 178 dogs were screened for Ehrlichiosis based on history, clinical signs, blood, and buffy coat [...] Read more.

The present study aimed to investigate pathological epidemiology and molecular confirmation of Ehrlichia canis among pet dogs in Bhubaneswar, Odisha, a state in eastern India. A total of 178 dogs were screened for Ehrlichiosis based on history, clinical signs, blood, and buffy coat smear examination, resulting in only 56 dogs (31.46%) screening positive. The epidemiological study recorded a non-significant (p ≥ 0.05) increase in incidences among male dogs (68%), German Shepherds (25%), dogs more than 20 kg body weight (75%), in the summer months (55%), and dogs housed in pukka houses with exposure to the outside (59%). The majority of the infected dogs had a history of tick infestation (79%) at some point in their lives. Clinical signs showed non-typical manifestations like fever, lethargy, diarrhoea, epistaxis, hind limb edema, and corneal opacity. Haematological studies revealed anaemia and thrombocytopenia along with neutrophilia with relative lymphopenia and monocytosis. A decreasing trend was observed in the levels of total protein and albumin, with an increase in the levels of globulin, alanine aminotransferase, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, and creatinine. The ultrasonography studies revealed hepatosplenomegaly along with hyper-echogenicity in various organs. Proteinuria and haematuria were consistent, along with the presence of bile salts in the urine of affected dogs. Molecular confirmation from n-type PCR data using Ehrlichia-specific primers targeting the p28 gene (843 bp) was done, and the identified gene sequences submitted to NCBI databases have accession numbers OQ383671-OQ383674 and OP886674-OP886677. Ticks collected from dogs were identified morphologically through microscopy and scanning electron microscopy as Rhipicephalus sanguineus. Full article

(This article belongs to the Special Issue Molecular Epidemiology of Pathogenic Agents)

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15 pages, 1247 KiB

Open AccessSystematic Review

Respiratory Syncytial Virus among People Living with HIV: Is There a Case for Rolling Out Prophylaxis? A Viewpoint Based on a Systematic Review

by André Almeida, Raffaele Aliberti, Arianna Aceti and Matteo Boattini

Pathogens 2024, 13(9), 802; https://doi.org/10.3390/pathogens13090802 - 16 Sep 2024

Respiratory Syncytial Virus (RSV) is responsible for a considerable burden of respiratory disease among children and older adults. Several prophylactic strategies have recently been introduced. We review the available evidence on the interplay between RSV infection and HIV, looking at the specific role [...] Read more.

Respiratory Syncytial Virus (RSV) is responsible for a considerable burden of respiratory disease among children and older adults. Several prophylactic strategies have recently been introduced. We review the available evidence on the interplay between RSV infection and HIV, looking at the specific role of RSV prophylactic strategies in individuals affected by or exposed to HIV. We conducted a systematic review on the association between HIV infection and RSV incidence and severity. We searched in PubMed/MEDLINE for clinical epidemiological studies covering outcomes such as RSV-associated illness, severity, and mortality in individuals affected by or exposed to HIV. A total of 36 studies met the inclusion criteria and were included, the majority conducted in sub-Saharan Africa. There was no compelling evidence suggesting a higher incidence of RSV illness among HIV-infected people. A higher risk of severe disease was consistent among both HIV-positive and HIV-exposed but uninfected (HEU) children. Case fatality rates were also higher for these groups. Evidence on a differing risk among adults was scarce. HIV-positive pregnant women should be given priority for recently approved RSV vaccination, for protection of their newborns. HIV-infected and HEU infants should be considered risk groups for nirsevimab prophylaxis in their first year of life and possibly beyond. Full article

(This article belongs to the Special Issue HIV/AIDS: Epidemiology, Drug Resistance, Treatment and Prevention)

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17 pages, 698 KiB

Open AccessReview

Gut Microbiota in Patients Receiving Dialysis: A Review

by Xintian Lim, Lijin Ooi, Uzhe Ding, Henry H. L. Wu and Rajkumar Chinnadurai

Pathogens 2024, 13(9), 801; https://doi.org/10.3390/pathogens13090801 - 15 Sep 2024

The human gut microbiota constitutes a complex community of microorganisms residing within the gastrointestinal tract, encompassing a vast array of species that play crucial roles in health and disease. The disease processes involved in chronic kidney disease (CKD) and end-stage kidney disease (ESKD) [...] Read more.

The human gut microbiota constitutes a complex community of microorganisms residing within the gastrointestinal tract, encompassing a vast array of species that play crucial roles in health and disease. The disease processes involved in chronic kidney disease (CKD) and end-stage kidney disease (ESKD) are now increasingly established to result in dysregulation of gut microbiota composition and function. Gut microbiota dysbiosis has been associated with poor clinical outcomes and all-cause mortality in patients with ESKD, particularly individuals receiving dialysis. Prior studies highlighted various factors that affect gut microbiota dysbiosis in CKD and ESKD. These include, but are not limited to, uraemic toxin accumulation, chronic inflammation, immune dysfunction, medications, and dietary restrictions and nutritional status. There is a lack of studies at present that focus on the evaluation of gut microbiota dysbiosis in the context of dialysis. Knowledge on gut microbiota changes in this context is important for determining their impact on dialysis-specific and overall outcomes for this patient cohort. More importantly, evaluating gut microbiota composition can provide information into potential targets for therapeutic intervention. Identification of specific microbial signatures may result in further development of personalised treatments to improve patient outcomes and mitigate complications during dialysis. Optimising gut microbiota through various therapeutic approaches, including dietary adjustments, probiotics, prebiotics, medications, and faecal transplantation, have previously demonstrated potential in multiple medical conditions. It remains to be seen whether these therapeutic approaches are effective within the dialysis setting. Our review aims to evaluate evidence relating to alterations in the gut microbiota of patients undergoing dialysis. A growing body of evidence pointing to the complex yet significant relationship which surrounds gut microbiota and kidney health emphasises the importance of gut microbial balance to improve outcomes for individuals receiving dialysis. Full article

(This article belongs to the Special Issue Molecular Epidemiology of Pathogenic Agents)

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14 pages, 2977 KiB

Open AccessArticle

HIV Modulates Osteoblast Differentiation via Upregulation of RANKL and Vitronectin

by Rosa Nicole Freiberger, Cynthia Alicia Marcela López, María Belén Palma, Cintia Cevallos, Franco Agustin Sviercz, Patricio Jarmoluk, Marcela Nilda García, Jorge Quarleri and M. Victoria Delpino

Pathogens 2024, 13(9), 800; https://doi.org/10.3390/pathogens13090800 - 15 Sep 2024

Bone loss is a prevalent characteristic among people with HIV (PWH). We focused on mesenchymal stem cells (MSCs) and osteoblasts, examining their susceptibility to different HIV strains (R5- and X4-tropic) and the subsequent effects on bone tissue homeostasis. Our findings suggest that MSCs [...] Read more.

Bone loss is a prevalent characteristic among people with HIV (PWH). We focused on mesenchymal stem cells (MSCs) and osteoblasts, examining their susceptibility to different HIV strains (R5- and X4-tropic) and the subsequent effects on bone tissue homeostasis. Our findings suggest that MSCs and osteoblasts are susceptible to R5- and X4-tropic HIV but do not support productive HIV replication. HIV exposure during the osteoblast differentiation process revealed that the virus could not alter mineral and organic matrix deposition. However, the reduction in runt-related transcription factor 2 (RUNX2) transcription, the increase in the transcription of nuclear receptor activator ligand kappa B (RANKL), and the augmentation of vitronectin deposition strongly suggested that X4- and R5-HIV could affect bone homeostasis. This study highlights the HIV ability to alter MSCs’ differentiation into osteoblasts, critical for maintaining bone and adipose tissue homeostasis and function. Full article

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

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16 pages, 1137 KiB

Open AccessArticle

Smells Like Anthelmintic Resistance—Gastrointestinal Prevalence, Burden and Diversity in Dogs from Portugal

by Cláudia Luís Batista, Ricardo Cabeças, Cláudio Araújo-Paredes, Maria Aires Pereira and Teresa Letra Mateus

Pathogens 2024, 13(9), 799; https://doi.org/10.3390/pathogens13090799 - 14 Sep 2024

Anthelmintic resistance has been documented worldwide, but few cases have been reported in dogs. Shelter dogs are a great opportunity to study intestinal helminths and assess their potential resistance to anthelmintic compounds. With these two goals in mind, 361 faecal samples were collected [...] Read more.

Anthelmintic resistance has been documented worldwide, but few cases have been reported in dogs. Shelter dogs are a great opportunity to study intestinal helminths and assess their potential resistance to anthelmintic compounds. With these two goals in mind, 361 faecal samples were collected from dogs in 18 municipalities in Portugal, from 19 shelters and 11 private tutors. These samples were analysed using the Mini-FLOTAC before and 13 days after deworming. The percentage of faecal egg count reduction was calculated. Parasitic forms were identified in 22.4% of the samples collected: Trichuris vulpis (10.5%), Toxocara canis (8.0%), members of the family Ancylostomatidae (6.4%), Toxascaris leonina (0.8%), Dipylidium caninum (0.6%) and members of the family Taeniidae (0.3%). The first three nematode parasites showed the highest intensity of infection (2900, 1325, and 1265 eggs per gram, respectively). In the second faecal collection, parasites were present in 20.8% of the samples. The anthelmintics febendazole + pyrantel embonate + praziquantel and praziquantel + fenbendazole were ineffective for T. vulpis and members of the family Ancylostomatidae in 16.2% and 6.9% of the samples, respectively. The parasites identified are all potentially zoonotic. This study is the first to suggest a potential resistance of T. vulpis to anthelmintics. Full article

(This article belongs to the Special Issue Parasitic Infections: Immunity, Vaccine and Drug Development)

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14 pages, 261 KiB

Open AccessArticle

Risk Factors for Salmonella Infection in Children under Five Years: A Hospital-Based Study in Kilimanjaro Region, Tanzania

by Ephrasia A. Hugho, Blandina T. Mmbaga, Abdul-Hamid S. Lukambagire, Grace D. Kinabo, Kate M. Thomas, Happiness H. Kumburu and Tine Hald

Pathogens 2024, 13(9), 798; https://doi.org/10.3390/pathogens13090798 - 14 Sep 2024

Salmonella is among the causative agents for diarrhea worldwide, but its risk factors in Tanzanian children are poorly understood. A hospital-based cross-sectional study was conducted in Moshi, Kilimanjaro region, from July 2020 to November 2022 among children under five admitted with diarrhea. A [...] Read more.

Salmonella is among the causative agents for diarrhea worldwide, but its risk factors in Tanzanian children are poorly understood. A hospital-based cross-sectional study was conducted in Moshi, Kilimanjaro region, from July 2020 to November 2022 among children under five admitted with diarrhea. A questionnaire was administered to all parents/caretakers of the enrolled children. Logistic regression was utilized to analyze the risk factors, with significance at p < 0.05. A total of 306 children were enrolled in the study. The median age was 13.8 months (IQR 8.4–21.8). The majority (58.5%) were males, and 59.5% were from rural areas. Salmonella was identified in eight (2.6%) stool samples, with a higher prevalence in urban than rural areas (4.8% vs. 1.1%; p-value = 0.044). The significant risk factors associated with Salmonella infection among the children included consuming raw milk (adjusted OR = 30.19; 95% CI: 3.94–231.46), using infant formula (adjusted OR = 15.78; 95% CI: 2.98–83.56), undisclosed household income (adjusted OR = 9.98; 95% CI: 2.46–40.12), purchasing eggs direct from the farms (adjusted OR = 7.58; 95%CI: 1.31–43.96), and contact with chickens (adjusted OR = 6.49; 95%CI: 1.25–33.59). These findings highlight the need for targeted interventions to improve food safety, hygiene practices, and socioeconomic conditions. Full article

14 pages, 2810 KiB

Open AccessArticle

Evaluation of the Antibacterial Potential of Two Short Linear Peptides YI12 and FK13 against Multidrug-Resistant Bacteria

by Jingyi Sun, Pan Kong, Jingru Shi and Yuan Liu

Pathogens 2024, 13(9), 797; https://doi.org/10.3390/pathogens13090797 - 14 Sep 2024

The accelerating spread of antibiotic resistance has significantly weakened the clinical efficacy of existing antibiotics, posing a severe threat to public health. There is an urgent need to develop novel antimicrobial alternatives that can bypass the mechanisms of antibiotic resistance and effectively kill [...] Read more.

The accelerating spread of antibiotic resistance has significantly weakened the clinical efficacy of existing antibiotics, posing a severe threat to public health. There is an urgent need to develop novel antimicrobial alternatives that can bypass the mechanisms of antibiotic resistance and effectively kill multidrug-resistant (MDR) pathogens. Antimicrobial peptides (AMPs) are one of the most promising candidates to treat MDR pathogenic infections since they display broad-spectrum antimicrobial activities and are less prone to achieve drug resistance. In this study, we investigated the antibacterial capability and mechanisms of two machine learning-driven linear peptide compounds termed YI12 and FK13. We reveal that YI12 and FK13 exhibit broad-spectrum antibacterial properties against clinically significant bacterial pathogens, inducing no or minimal hemolysis in mammalian red blood cells. We further ascertain that YI12 and FK13 are resilient to heat and acid-base conditions, and exhibit susceptibility to hydrolytic enzymes and divalent cations under physiological conditions. Initial mechanistic investigations reveal that YI12 and FK13 compromise bacterial membrane integrity, leading to membrane potential dissipation and excessive reactive oxygen species (ROS) generation. Collectively, our findings highlight the prospective utility of these two cationic amphiphilic peptides as broad-spectrum antibacterial agents. Full article

(This article belongs to the Special Issue New Approaches to Combating Multidrug-Resistant Pathogens)

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13 pages, 1656 KiB

Open AccessArticle

Metabolic Footprint of Treponema phagedenis and Treponema pedis Reveals Potential Interaction Towards Community Succession and Pathogenesis in Bovine Digital Dermatitis

by Hector M. Espiritu, Edeneil Jerome P. Valete, Lovelia L. Mamuad, Myunghwan Jung, Man-Jeong Paik, Sang-Suk Lee and Yong-Il Cho

Pathogens 2024, 13(9), 796; https://doi.org/10.3390/pathogens13090796 - 14 Sep 2024

Bovine digital dermatitis (BDD) is a cattle infection causing hoof lesions and lameness, with treponemes as key pathogens. We analyzed the metabolic activity of Treponema phagedenis and Treponema pedis using gas chromatography–mass spectrometry for organic acids (OAs), amino acids (AAs), and fatty acids [...] Read more.

Bovine digital dermatitis (BDD) is a cattle infection causing hoof lesions and lameness, with treponemes as key pathogens. We analyzed the metabolic activity of Treponema phagedenis and Treponema pedis using gas chromatography–mass spectrometry for organic acids (OAs), amino acids (AAs), and fatty acids (FAs), and high-performance liquid chromatography for short-chain fatty acids (SCFAs). Key findings include a 61.5% reduction in pyruvic acid in T. pedis and 81.0% in T. phagedenis. 2-hydroxybutyric acid increased by 493.8% in T. pedis, while succinic acid increased by 31.3%, potentially supporting T. phagedenis. Among AAs, glycine was reduced by 97.4% in T. pedis but increased by 64.1% in T. phagedenis. Proline increased by 76.6% in T. pedis but decreased by 13.6% in T. phagedenis. Methionine and glutamic acid were competitively utilized, with methionine reduced by 41.8% in T. pedis and 11.9% in T. phagedenis. Both species showed significant utilization of palmitic acid (reduced by 82.8% in T. pedis and 87.2% in T. phagedenis). Butyric acid production increased by 620.2% in T. phagedenis, and propionic acid increased by 932.8% in T. pedis and 395.6% in T. phagedenis. These reveal metabolic interactions between the pathogens, contributing to disease progression and offering insights to BDD pathogenesis. Full article

(This article belongs to the Section Bacterial Pathogens)

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22 pages, 1251 KiB

Open AccessFeature PaperArticle

Characterising the Metabolomic Diversity and Biological Potentials of Extracts from Different Parts of Two Cistus Species Using UHPLC-MS/MS and In Vitro Techniques

by Shakeel Ahmed, Gokhan Zengin, Selami Selvi, Gunes Ak, Zoltán Cziáky, József Jekő, Maria J. Rodrigues, Luisa Custodio, Roberto Venanzoni, Giancarlo Angeles Flores, Gaia Cusumano and Paola Angelini

Pathogens 2024, 13(9), 795; https://doi.org/10.3390/pathogens13090795 - 13 Sep 2024

This study investigates the biochemical composition and biological properties of different parts (leaves, roots, and twigs) of two Cistus species (Cistus monspeliasis and Cistus parviflorus). The extracts were analysed using UHPLC-MS/MS to determine their chemical profiling. A range of antioxidant assays [...] Read more.

This study investigates the biochemical composition and biological properties of different parts (leaves, roots, and twigs) of two Cistus species (Cistus monspeliasis and Cistus parviflorus). The extracts were analysed using UHPLC-MS/MS to determine their chemical profiling. A range of antioxidant assays were performed to evaluate the extract’s antioxidant capabilities. The enzyme inhibition studies focused on acetylcholinesterase (AChE), butyrylcholinesterase (BChE), α-amylase, and α-glucosidase and tyrosinase. In addition, the study examined the antimicrobial effects on different bacteria and yeasts and evaluated the toxicity using the MTT assay. Quinic acid, citric acid, gallic acid, catechin, quercetin derivatives, kaempferol, myricetin, ellagic acid, prodelphinidins, procyanidins, scopoletin, and flavogallonic acid dilactone are the main bioactive compounds found in both species. In enzyme inhibition assays, C. monspeliasis roots exhibited significant activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), with the values of 2.58 ± 0.02 mg GALAE/g and 11.37 ± 1.93 mg GALAE/g, respectively. Cytotoxicity studies showed mostly weak toxicity, with some samples moderately reducing viability in RAW and HepG2 cells. These findings underscore the diverse biochemical profiles and bioactive potential of Cistus species, suggesting their utility as natural sources of antioxidants and enzyme inhibitors for pharmaceutical and nutraceutical development. Full article

(This article belongs to the Section Fungal Pathogens)

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22 pages, 976 KiB

Open AccessArticle

Comprehensive Genomic Analysis of Uropathogenic E. coli: Virulence Factors, Antimicrobial Resistance, and Mobile Genetic Elements

by Kidon Sung, Mohamed Nawaz, Miseon Park, Jungwhan Chon, Saeed A. Khan, Khulud Alotaibi and Ashraf A. Khan

Pathogens 2024, 13(9), 794; https://doi.org/10.3390/pathogens13090794 - 13 Sep 2024

Our whole-genome sequencing analysis of sixteen uropathogenic E. coli isolates revealed a concerning picture of multidrug resistance and potentially virulent bacteria. All isolates belonged to four distinct clonal groups, with the highly prevalent ST131 lineage being associated with extensive antibiotic resistance and virulence [...] Read more.

Our whole-genome sequencing analysis of sixteen uropathogenic E. coli isolates revealed a concerning picture of multidrug resistance and potentially virulent bacteria. All isolates belonged to four distinct clonal groups, with the highly prevalent ST131 lineage being associated with extensive antibiotic resistance and virulence factors. Notably, all isolates exhibited multidrug resistance, with some resistant to as many as 12 antibiotics. Fluoroquinolone resistance stemmed primarily from efflux pumps and mutations in gyrase and topoisomerase genes. Additionally, we identified genes encoding resistance to extended-spectrum cephalosporins, trimethoprim/sulfamethoxazole, and various heavy metals. The presence of diverse plasmids and phages suggests the potential for horizontal gene transfer and the dissemination of virulence factors. All isolates harbored genomic islands containing virulence factors associated with adhesion, biofilm formation, and invasion. Genes essential for iron acquisition, flagella biosynthesis, secretion systems, and toxin production were also prevalent. Adding further complexity to understanding the isolates’ genetic makeup, we identified CRISPR-Cas systems. This study underscores the need for continued genomic surveillance in understanding the pathogenic mechanisms and resistance profiles of uropathogenic E. coli to aid in developing targeted therapeutic strategies. Full article

(This article belongs to the Special Issue Antimicrobial Resistance of Pathogens Causing Nosocomial Infections)

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18 pages, 4536 KiB

Open AccessArticle

Molecular Epidemiology of Hepatitis D Virus in the North-East Region of Romania

by Laura Iulia Grecu, Mariana Pavel-Tanasa, Lilia Matei, Camelia Sultana, Simona Maria Ruta, Razvan Ioan Grecu, Ramona Gabriela Ursu, Petru Cianga and Luminita Smaranda Iancu

Pathogens 2024, 13(9), 793; https://doi.org/10.3390/pathogens13090793 - 13 Sep 2024

The hepatitis D virus (HDV) superinfection of individuals with chronic hepatitis B virus (HBV) infection causes severe liver damage and the poorest long-term prognosis among viral hepatitis. This is attributed to the unique pathogenic mechanisms of HDV characterized by a direct cytopathic effect [...] Read more.

The hepatitis D virus (HDV) superinfection of individuals with chronic hepatitis B virus (HBV) infection causes severe liver damage and the poorest long-term prognosis among viral hepatitis. This is attributed to the unique pathogenic mechanisms of HDV characterized by a direct cytopathic effect on hepatocytes and a significant impairment of the host immune response. The HDV genotype largely influences the extent of the pathogenic mechanisms with consequences on disease progression towards cirrhosis, liver decompensation, or hepatocellular carcinoma. In this context, identifying the circulating HDV genotypes in European regions with high prevalence, such as Romania, is crucial for effectively managing the long-term liver health. Here, we report the first comprehensive HDV study in Romania that clinically characterizes 82 patients and performs HDV genotyping by combining the nested-PCR reaction with sequencing analysis in 49 samples with an HDV-RNA load higher than 5000 IU/mL. While all isolates in our study belong to the HDV-1 genotype, the phylogenetic analysis based on sequence data from GenBank reveals the presence of the following potential three groups: (i) Italy and France; (ii) Spain; and (iii) Turkey, Iran, Pakistan, and Germany. This broad clustering highlights the recent surge in migration to and from Western Europe and the Middle East. Equally important, no differences in viral markers, clinical and paraclinical parameters, or treatment options were observed between these identified clusters. Nevertheless, this study considerably advances the understanding of hepatitis D epidemiology and clinical aspects in Romania. Full article

(This article belongs to the Special Issue Oncogenic Viruses: Advances in Molecular Diagnosis, Prevention Strategies and Therapy)

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11 pages, 964 KiB

Open AccessArticle

Diagnostic Pathways of Leptospira spp. in Dogs with Kidney Injury

by Ioan Hutu, Oana Maria Boldura, Iasmina Luca, Sorin Aurelian Pasca, Alina Andreea Dragoescu, Radu Valentin Gros, Bianca Cornelia Lungu, Andrei Călugăriță, Cornel Baltă, Călin Mircu and Adrian Constantin Stancu

Pathogens 2024, 13(9), 792; https://doi.org/10.3390/pathogens13090792 - 12 Sep 2024

Pathogenic Leptospira spp. causes leptospirosis in animals and humans globally, leading to systemic infections that can impact vital organs in affected animals. The purpose of this study was to evaluate kidney injury and to perform a retrospective analysis of leptospirosis infection in follow-up [...] Read more.

Pathogenic Leptospira spp. causes leptospirosis in animals and humans globally, leading to systemic infections that can impact vital organs in affected animals. The purpose of this study was to evaluate kidney injury and to perform a retrospective analysis of leptospirosis infection in follow-up dog samples. The retrospective study collected epidemiological information obtained through paraclinical exams, immunohistochemistry (IHC), and molecular biology (qPCR) of cases from the Faculty of Veterinary Medicine from Timisoara between September 2016 and May 2023. No correlations were found between Leptospira infection and breed (p = 0.714), gender or castration status (p = 0.890), and anatomic pathology exam results (p = 0.608). Significant associations were found in cases with high levels of azotemia (p = 0.000) and immunological status (vaccinated vs. unvaccinated, p = 0.000), with the leptospirosis risk in unvaccinated animals calculated at OR = 85.500 (95%CI, 6.82–1071.26, p = 0.000). Retrospectively, leptospirosis was diagnosed in 27/65 cases (42%) using the IHC method, while the qPCR assay detected 29/65 cases (45%). This study demonstrates that qPCR is a robust and specific method for postmortem diagnosis of Leptospira spp. infection in dogs, offering higher specificity and reliability compared to traditional IHC methods, which showed 94.74% specificity in our study. Full article

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14 pages, 1404 KiB

Open AccessArticle

Role of Poly(A)-Binding Protein Cytoplasmic 1, a tRNA-Derived RNA Fragment-Bound Protein, in Respiratory Syncytial Virus Infection

by Devin V. Davis, Eun-Jin Choi, Deena Ismail, Miranda L. Hernandez, Jong Min Choi, Ke Zhang, Kashish Khatkar, Sung Yun Jung, Wenzhe Wu and Xiaoyong Bao

Pathogens 2024, 13(9), 791; https://doi.org/10.3390/pathogens13090791 - 12 Sep 2024

Respiratory Syncytial Virus (RSV) is a significant cause of lower respiratory tract infections (LRTI) across all demographics, with increasing mortality and morbidity among high-risk groups such as infants under two years old, the elderly, and immunocompromised individuals. Although newly approved vaccines and treatments [...] Read more.

Respiratory Syncytial Virus (RSV) is a significant cause of lower respiratory tract infections (LRTI) across all demographics, with increasing mortality and morbidity among high-risk groups such as infants under two years old, the elderly, and immunocompromised individuals. Although newly approved vaccines and treatments have substantially reduced RSV hospitalizations, accessibility remains limited, and response to treatment varies. This underscores the importance of comprehensive studies on host–RSV interactions. tRNA-derived RNA fragments (tRFs) are recently discovered non-coding RNAs, notable for their regulatory roles in diseases, including viral infections. Our prior work demonstrated that RSV infection induces tRFs, primarily derived from the 5′-end of a limited subset of tRNAs (tRF5), to promote RSV replication by partially targeting the mRNA of antiviral genes. This study found that tRFs could also use their bound proteins to regulate replication. Our proteomics data identified that PABPC1 (poly(A)-binding protein cytoplasmic 1) is associated with tRF5-GluCTC, an RSV-induced tRF. Western blot experimentally confirmed the presence of PABPC1 in the tRF5-GluCTC complex. In addition, tRF5-GluCTC is in the anti-PABPC1-precipitated immune complex. This study also discovered that suppressing PABPC1 with its specific siRNA increased RSV (-) genome copies without impacting viral gene transcription, but led to less infectious progeny viruses, suggesting the importance of PABPC1 in virus assembly, which was supported by its interaction with the RSV matrix protein. Additionally, PABPC1 knockdown decreased the production of the cytokines MIP-1α, MIP-1β, MCP-1, and TNF-α. This is the first observation suggesting that tRFs may regulate viral infection via their bound proteins. Full article

(This article belongs to the Section Viral Pathogens)

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19 pages, 8485 KiB

Open AccessArticle

Evaluation of the In-Vitro Effects of Albendazole, Mebendazole, and Praziquantel Nanocapsules against Protoscolices of Hydatid Cyst

by Nooshinmehr Soleymani, Soheil Sadr, Cinzia Santucciu, Abbas Rahdar, Giovanna Masala and Hassan Borji

Pathogens 2024, 13(9), 790; https://doi.org/10.3390/pathogens13090790 - 12 Sep 2024

Cystic echinococcosis still remains a serious health and economic problem worldwide. The etiologic agent is Echinococcus granulosus sensu lato, giving origin to a fluid-filled cystic lesion. Therapy faces several challenges. Nanodrugs have shown promise as chemotherapeutics against hydatid cysts. The present study [...] Read more.

Cystic echinococcosis still remains a serious health and economic problem worldwide. The etiologic agent is Echinococcus granulosus sensu lato, giving origin to a fluid-filled cystic lesion. Therapy faces several challenges. Nanodrugs have shown promise as chemotherapeutics against hydatid cysts. The present study evaluated a highly safe lipid nano-polymeric capsule for its superior efficacy and ability to overcome drug resistance. Nanocapsule drugs were formulated into six groups: Albendazole, mebendazole, praziquantel, albendazole + mebendazole, albendazole + praziquantel, and praziquantel + mebendazole. The protoscolicidal effects of these six groups were assessed at 10, 60, and 120 min in three concentrations (1, 0.5, and 0.25 mg/mL). Drug formulations were evaluated via zeta potential, droplet size, solubility, particle size analyzer (PSA), and scanning electron microscopy. According to the PSA results, the mean size of the albendazole nanocapsules was 193.01 nm, mebendazole was 170.40 nm, and praziquantel was 180.44 nm. Albendazole + mebendazole showed the greatest protoscolicidal activity at a concentration of 1 mg/mL after 120 min. In contrast, each drug’s 0.25 mg/mL single-dose times showed the least protoscolicidal activity after 120 min. With the right application of nanotechnology, it is possible to produce safe and effective drugs, such as the polymeric combination of albendazole and mebendazole, which has promising implications. Full article

(This article belongs to the Section Parasitic Pathogens)

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