Pathogens

12 pages, 1721 KiB

Open AccessEditor’s ChoiceArticle

MultiTEP-Based Vaccines Targeting SARS-CoV-2 Spike Protein IgG Epitopes Elicit Robust Binding Antibody Titers with Limited Virus-Neutralizing Activity

by Tatevik Antonyan, Garri Chilingaryan, Karen Zagorski, Manush Ghazaryan, Armine Hovakimyan, Hayk Davtyan, Irina Petrushina, Olga King, Roman Kniazev, Nikolai Petrovsky and Anahit Ghochikyan

Pathogens 2024, 13(6), 520; https://doi.org/10.3390/pathogens13060520 - 20 Jun 2024

Viewed by 1184

Abstract

Within the last two decades, SARS-CoV-2 was the third zoonotic severe acute respiratory betacoronavirus (sarbecovirus) to infect humans, following SARS and MERS. The disruptions caused by the pandemic underscore the need for a universal vaccine against respiratory betacoronaviruses. Our group previously developed the [...] Read more.

Within the last two decades, SARS-CoV-2 was the third zoonotic severe acute respiratory betacoronavirus (sarbecovirus) to infect humans, following SARS and MERS. The disruptions caused by the pandemic underscore the need for a universal vaccine against respiratory betacoronaviruses. Our group previously developed the universal platform for vaccine development, MultiTEP, which has been utilized in this study to generate a range of SARS-CoV-2 epitope vaccine candidates. We prepared and characterized 18 vaccines incorporating small peptide fragments from SARS-CoV-2 Spike protein fused with the MultiTEP sequence using overlapping PCR. Wild-type mice were immunized intramuscularly with the immunogen formulated in AdvaxCpG adjuvant. Serum antibodies were detected by ELISA, surrogate neutralization, and pseudovirus neutralization assays. Finally, the most promising vaccine candidate was administered to three non-human primates. All vaccines generated high titers of spike-binding IgG antibodies. However, only three vaccines generated antibodies that blocked RBD binding to the ACE2 receptor in a surrogate virus neutralization assay. However, none of the vaccines induced antibodies able to neutralize pseudotype viruses, including after the administration of the lead vaccine to NHPs. MultiTEP-based COVID-19 vaccines elicited robust, IgG-binding responses against the Spike protein in mice and non-human primates, but these antibodies were not neutralizing, underscoring the need to refine this approach further. Full article

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12 pages, 1504 KiB

Open AccessEditor’s ChoiceArticle

Differential Gene Expression in the Upper Respiratory Tract following Acute COVID-19 Infection in Ambulatory Patients That Develop Long COVID

by Mia J. Biondi, Mary Addo, Muhammad Atif Zahoor, Elsa Salvant, Paul Yip, Bethany Barber, David Smookler, Sumaiyah Wasif, Kayla Gaete, Christopher Kandel, Jordan J. Feld, Hubert Tsui and Robert A. Kozak

Pathogens 2024, 13(6), 510; https://doi.org/10.3390/pathogens13060510 - 17 Jun 2024

Viewed by 2311

Abstract

Background: Post-acute sequelae of COVID-19, or long COVID, is a condition characterized by persistent COVID-19 symptoms. As long COVID is defined by clinical criteria after an elapsed period, an opportunity for early intervention may aid in future prophylactic approaches; however, at present, the [...] Read more.

Background: Post-acute sequelae of COVID-19, or long COVID, is a condition characterized by persistent COVID-19 symptoms. As long COVID is defined by clinical criteria after an elapsed period, an opportunity for early intervention may aid in future prophylactic approaches; however, at present, the pathobiological mechanisms are multifactorial. By analyzing early virally infected upper respiratory tract tissue prior to eventual clinical diagnosis, it may be possible to identify biomarkers of altered immune response to facilitate future studies and interventions. Methods: This is a sub-group analysis of samples collected from those with confirmed COVID-19. RNA extraction from nasopharyngeal/mid-turbinate samples, sequencing, and bioinformatic analysis were performed to analyze long COVID and non-long COVID cohorts at day 14 post infection. Differences in mean viral load at various timepoints were analyzed as well as serological data. Results: We identified 26 upregulated genes in patients experiencing long COVID. Dysregulated pathways including complement and fibrinolysis pathways and IL-7 upregulation. Additionally, genes involved in neurotransmission were dysregulated, and the long COVID group had a significantly higher viral load and slower viral clearance. Conclusions: Uncovering early gene pathway abnormalities associated with eventual long COVID diagnosis may aid in early identification. We show that, post acute infection, in situ pathogenic deviations in viral response are associated with patients destined to meet consensus long COVID diagnosis that is entirely dependent on clinical factors. These results identify an important biological temporal window in the natural history of COVID-19 infection and long COVID pathogenesis amenable to testing from standard-of-care upper respiratory tract specimens. Full article

(This article belongs to the Section Viral Pathogens)

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15 pages, 1364 KiB

Open AccessEditor’s ChoiceArticle

Cytomegalovirus, Epstein-Barr Virus, Herpes Simplex Virus, and Varicella Zoster Virus Infection Dynamics in People with Multiple Sclerosis from Northern Italy

by Peter A. Maple, Radu Tanasescu, Cris S. Constantinescu, Paola Valentino, Marco Capobianco, Silvia D’Orso, Giovanna Borsellino, Luca Battistini, Giovanni Ristori, Rosella Mechelli, Marco Salvetti and Bruno Gran

Pathogens 2024, 13(6), 499; https://doi.org/10.3390/pathogens13060499 - 12 Jun 2024

Viewed by 1473

Abstract

Previous exposure to Epstein–Barr virus (EBV) is strongly associated with the development of multiple sclerosis (MS). By contrast, past cytomegalovirus (CMV) infection may have no association, or be negatively associated with MS. This study aimed to investigate the associations of herpesvirus infections with [...] Read more.

Previous exposure to Epstein–Barr virus (EBV) is strongly associated with the development of multiple sclerosis (MS). By contrast, past cytomegalovirus (CMV) infection may have no association, or be negatively associated with MS. This study aimed to investigate the associations of herpesvirus infections with MS in an Italian population. Serum samples (n = 200) from Italian people with multiple sclerosis (PwMS) classified as the relapsing-and-remitting clinical phenotype and (n = 137) healthy controls (HCs) were obtained from the CRESM Biobank, Orbassano, Italy. Both PwMS and HCs samples were selected according to age group (20–39 years, and 40 or more years) and sex. EBV virus capsid antigen (VCA) IgG, EBV nucleic acid-1 antigen (EBNA-1) IgG, CMV IgG, herpes simplex virus (HSV) IgG, and varicella zoster virus (VZV) IgG testing was undertaken using commercial ELISAs. EBV VCA IgG and EBNA-1 IgG seroprevalences were 100% in PwMS and 93.4% and 92.4%, respectively, in HCs. EBV VCA IgG and EBNA-1 IgG levels were higher (p < 0.001) in PwMS compared with HCs. For PwMS, the EBNA-1 IgG levels decreased with age, particularly in females. The CMV IgG seroprevalence was 58.7% in PwMS and 62.9% in HCs. CMV IgG seroprevalence increased with age. The HSV IgG seroprevalence was 71.2% in PwMS and 70.8% in HCs. HSV IgG levels were lower (p = 0.0005) in PwMS compared with HCs. VZV IgG seroprevalence was 97.5% in PwMS and 98.5% in HCs. In the population studied, several herpesvirus infections markers may have been influenced by the age and sex of the groups studied. The lack of a negative association of MS with CMV infection, and the observation of lower levels of HSV IgG in PwMS compared with HCs are findings worthy of further investigation. Full article

(This article belongs to the Special Issue Viral Infections and Their Effects on the Central Nervous System (CNS))

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13 pages, 1980 KiB

Open AccessEditor’s ChoiceArticle

Prevalence and Control of Pseudomonas aeruginosa in Tourist Facilities across the Canary Islands, Spain

by Antonio Doménech-Sánchez, Elena Laso and Sebastián Albertí

Pathogens 2024, 13(6), 501; https://doi.org/10.3390/pathogens13060501 - 12 Jun 2024

Viewed by 1215

Abstract

Pseudomonas aeruginosa is a common pathogen associated with recreational water facilities and poses risks to public health. However, data on the prevalence of P. aeruginosa in tourist destinations like the Canary Islands, Spain, remain limited. We assessed P. aeruginosa prevalence in 23 tourist [...] Read more.

Pseudomonas aeruginosa is a common pathogen associated with recreational water facilities and poses risks to public health. However, data on the prevalence of P. aeruginosa in tourist destinations like the Canary Islands, Spain, remain limited. We assessed P. aeruginosa prevalence in 23 tourist facilities from 2016 to 2019. Compliance with water quality standards was evaluated, and 3962 samples were collected and analyzed. We examined different types of recreational water installations, including outer swimming pools, whirlpools, and cold wells. Of the sampled facilities, 31.2% did not comply with the current legislation’s parametric values, mainly due to inadequate disinfectant levels, water temperature, and P. aeruginosa presence. The prevalence of P. aeruginosa was 4.8%, comparable to some European countries but lower than others. Cold wells displayed the highest non-compliance rate (89.2%) and yet exhibited a lower P. aeruginosa prevalence (1.9%) than outer swimming pools and whirlpools. Children’s presence did not significantly impact P. aeruginosa contamination. Chlorine-based disinfectants are more effective than bromine-based ones in controlling P. aeruginosa. Regional variability in contamination was observed, with Fuerteventura showing lower colonization rates. Disinfectant levels play a critical role in P. aeruginosa control, and maintaining adequate levels is essential, particularly in bromine-treated installations. Our findings provide valuable insights into the prevalence and distribution of P. aeruginosa in recreational waters within tourist facilities. Tailored strategies are needed to ensure water safety in different Spanish regions. Continued monitoring and assessment, combined with artificial intelligence and machine learning, will enable the implementation of targeted interventions to protect the health of recreational water users. Full article

(This article belongs to the Section Bacterial Pathogens)

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31 pages, 4290 KiB

Open AccessEditor’s ChoiceReview

Brief Insights into mRNA Vaccines: Their Successful Production and Nanoformulation for Effective Response against COVID-19 and Their Potential Success for Influenza A and B

by Amerah Parveen and Amal Ali Elkordy

Pathogens 2024, 13(6), 500; https://doi.org/10.3390/pathogens13060500 - 12 Jun 2024

Viewed by 1981

Abstract

A mRNA vaccine is a type of vaccine that induces an immune response. Antigen-encoding mRNA is delivered via vaccine carriers into the immune cells, which are produced because of antigen-encoding mRNA translation, a protein. For example, COVID-19 mRNA vaccines produce the spike protein [...] Read more.

A mRNA vaccine is a type of vaccine that induces an immune response. Antigen-encoding mRNA is delivered via vaccine carriers into the immune cells, which are produced because of antigen-encoding mRNA translation, a protein. For example, COVID-19 mRNA vaccines produce the spike protein of the COVID-19 virus, whereas for influenza virus, mRNA vaccines target the haemagglutinin protein to treat the flu, and it requires modifications depending on the pandemic or seasonal viruses as it is capable of adapting the immune response, which makes the development of vaccines arduous. The protein molecule promotes an adaptive immune response that eliminates and terminates the corresponding virus or pathogen. There are many challenges to delivering an mRNA vaccine into the body; hence, the encapsulation of the mRNA (usually within lipid nanoparticles) is necessary to protect the mRNA from the body’s surrounding environment. In this review article, we focus mainly on the production, formulation, and stabilization of mRNA vaccines in general, elaborating more on and focusing more on SARS-CoV-2, or COVID-19, and influenza viruses, which have become a major concern as these viruses have turned into life-threatening diseases. Full article

(This article belongs to the Special Issue Advance in Influenza A and Influenza B Viruses)

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19 pages, 3010 KiB

Open AccessEditor’s ChoiceReview

Congenital Syphilis: A Re-Emerging but Preventable Infection

by Serena Salomè, Maria Donata Cambriglia, Giovanna Montesano, Letizia Capasso and Francesco Raimondi

Pathogens 2024, 13(6), 481; https://doi.org/10.3390/pathogens13060481 - 6 Jun 2024

Viewed by 2255

Abstract

Congenital syphilis presents a significant global burden, contributing to fetal loss, stillbirth, neonatal mortality, and congenital infection. Despite the target established in 2007 by the World Health Organization (WHO) of fewer than 50 cases per 100,000 live births, the global incidence is on [...] Read more.

Congenital syphilis presents a significant global burden, contributing to fetal loss, stillbirth, neonatal mortality, and congenital infection. Despite the target established in 2007 by the World Health Organization (WHO) of fewer than 50 cases per 100,000 live births, the global incidence is on the rise, particularly in low- and middle-income regions. Recent data indicate a rate of 473 cases per 100,000 live births, resulting in 661,000 total cases of congenital syphilis, including 355,000 adverse birth outcomes such as early fetal deaths, stillbirths, neonatal deaths, preterm or low-birth-weight births, and infants with clinical congenital syphilis. Alarmingly, only 6% of these adverse outcomes occurred in mothers who were enrolled, screened, and treated. Unlike many neonatal infections, congenital syphilis is preventable through effective antenatal screening and treatment of infected pregnant women. However, despite available screening tools, affordable treatment options, and the integration of prevention programs into antenatal care in various countries, congenital syphilis remains a pressing public health concern worldwide. This review aims to summarize the current epidemiology, transmission, and treatment of syphilis in pregnancy, as well as to explore global efforts to reduce vertical transmission and address the reasons for falling short of the WHO elimination target. Full article

(This article belongs to the Special Issue Emerging and Re-emerging Infections in Pediatrics)

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13 pages, 411 KiB

Open AccessEditor’s ChoiceArticle

Comparing Occurrence of Bovine Respiratory Pathogens Detected by High-Throughput Real-Time PCR in Nasal Swabs and Non-Endoscopic Bronchoalveolar Lavage Samples from Dairy and Veal Calves

by Nina Dam Otten, Nicole Bakkegård Goecke, Anne Marie Michelsen, Liza Rosenbaum Nielsen, Nynne Capion, Henrik Læssøe Martin, Bodil Højlund Nielsen, Lars Erik Larsen and Mette Bisgaard Petersen

Pathogens 2024, 13(6), 479; https://doi.org/10.3390/pathogens13060479 - 5 Jun 2024

Viewed by 1201

Abstract

This study aimed to enhance our understanding of the agreement between two sampling methods for the detection of bovine respiratory disease (BRD) pathogens in calves using high-throughput real-time qPCR (ht-RT-qPCR). In total, 233 paired nasal swab (NS) and non-endoscopic bronchoalveolar lavage (nBAL) samples [...] Read more.

This study aimed to enhance our understanding of the agreement between two sampling methods for the detection of bovine respiratory disease (BRD) pathogens in calves using high-throughput real-time qPCR (ht-RT-qPCR). In total, 233 paired nasal swab (NS) and non-endoscopic bronchoalveolar lavage (nBAL) samples were collected from 152 calves from 12 Danish cattle herds. In 202 of the observations, the calves were examined using a standardized clinical protocol. Samples were tested for three viruses (bovine respiratory syncytial virus, bovine corona virus, and influenza D virus) and six bacteria (Histophilus somni, Mannheimia haemolytica, Mycoplasma bovis, Mycoplasma species, Pasteurella multocida, and Truepurella pyogenes). The results showed age-related differences in disease and pathogen occurrence, with the highest detection rates in calves aged 35 days or older. Poor to moderate agreement was found between the NS and nBAL results. The presence of Mannheimia haemolytica in both NS and nBAL in younger calves and in nBAL in older calves was associated with clinical BRD. There was a potential link between BRD and influenza D virus in older calves, although it was only found in one herd in a small sample size. Overall, NS was a relatively poor predictor of pathogens in the lower respiratory tract. The present study confirms the complexity of pathogen detection in BRD, with marked influences of age and the sampling method on pathogen detection and disease associations. Full article

(This article belongs to the Special Issue Mycoplasmas in Respiratory Tract Infections of Cattle)

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14 pages, 2270 KiB

Open AccessEditor’s ChoiceArticle

Sex Differences during Influenza A Virus Infection and Vaccination and Comparison of Cytokine and Antibody Responses between Plasma and Serum Samples

by Santosh Dhakal, Brian W. Wolfe, Saurav Pantha and Saranya Vijayakumar

Pathogens 2024, 13(6), 468; https://doi.org/10.3390/pathogens13060468 - 1 Jun 2024

Viewed by 1195

Abstract

In this study, we evaluated sex differences during infection with mouse-adapted H1N1 and H3N2 influenza A viruses (IAVs) in the C57BL/6J mouse model and compared the cytokine and antibody responses between plasma and serum samples during IAV infection and vaccination. Lethal doses for [...] Read more.

In this study, we evaluated sex differences during infection with mouse-adapted H1N1 and H3N2 influenza A viruses (IAVs) in the C57BL/6J mouse model and compared the cytokine and antibody responses between plasma and serum samples during IAV infection and vaccination. Lethal doses for both H1N1 and H3N2 IAVs were lower for adult females and they suffered with greater morbidity than adult males when infected with sublethal doses. In influenza virus-infected mice, cytokine responses differed between plasma and serum samples. After inactivated influenza virus vaccination and drift variant challenge, adult female mice had greater antibody responses and were better protected. In influenza-vaccinated and challenged mice, binding antibodies were unaffected between paired plasma or serum samples. However, functional antibody assays, including hemagglutination inhibition, microneutralization, and antibody-dependent cellular cytotoxicity assays, were affected by the use of plasma and serum sample types. Our results indicate that careful consideration is required while selecting plasma versus serum samples to measure cytokine and antibody responses during IAV infection and vaccination. Full article

(This article belongs to the Special Issue Immunity to Respiratory Infections)

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16 pages, 359 KiB

Open AccessEditor’s ChoiceReview

Hospital Acquired Sepsis, Disease Prevalence, and Recent Advances in Sepsis Mitigation

by Mary Garvey

Pathogens 2024, 13(6), 461; https://doi.org/10.3390/pathogens13060461 - 30 May 2024

Cited by 1 | Viewed by 2338

Abstract

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, commonly associated with nosocomial transmission. Gram-negative bacterial species are particularly problematic due to the release of the lipopolysaccharide toxins upon cell death. The lipopolysaccharide toxin of E. coli has [...] Read more.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, commonly associated with nosocomial transmission. Gram-negative bacterial species are particularly problematic due to the release of the lipopolysaccharide toxins upon cell death. The lipopolysaccharide toxin of E. coli has a greater immunogenic potential than that of other Gram-negative bacteria. The resultant dysregulation of the immune system is associated with organ failure and mortality, with pregnant women, ICU patients, and neonates being particularly vulnerable. Additionally, sepsis recovery patients have an increased risk of re-hospitalisation, chronic illness, co-morbidities, organ damage/failure, and a reduced life expectancy. The emergence and increasing prevalence of antimicrobial resistance in bacterial and fungal species has impacted the treatment of sepsis patients, leading to increasing mortality rates. Multidrug resistant pathogens including vancomycin-resistant Enterococcus, beta lactam-resistant Klebsiella, and carbapenem-resistant Acinetobacter species are associated with an increased risk of mortality. To improve the prognosis of sepsis patients, predominantly high-risk neonates, advances must be made in the early diagnosis, triage, and control of sepsis. The identification of suitable biomarkers and biomarker combinations, coupled with machine learning and artificial intelligence, show promise in early detection protocols. Rapid diagnosis of sepsis in patients is essential to inform on clinical treatment, especially with resistant infectious agents. This timely review aims to discuss sepsis prevalence, aetiology, and recent advances towards disease mitigation and control. Full article

(This article belongs to the Special Issue Nosocomial Infection and Antimicrobial Resistance)

13 pages, 2088 KiB

Open AccessEditor’s ChoiceArticle

Pathogens Detected in Questing Ixodes ricinus Ticks in a Mountainous Area in Greece

by Katerina Tsioka, Anastasios Saratsis, Styliani Pappa and Anna Papa

Pathogens 2024, 13(6), 449; https://doi.org/10.3390/pathogens13060449 - 25 May 2024

Viewed by 1448

Abstract

Ixodes ricinus ticks are vectors of a plethora of pathogens. The purpose of this study was to screen 398 I. ricinus ticks for a variety of pathogens. Following the pooling, homogenization, and extraction of total nucleic acids, a real-time PCR was applied for [...] Read more.

Ixodes ricinus ticks are vectors of a plethora of pathogens. The purpose of this study was to screen 398 I. ricinus ticks for a variety of pathogens. Following the pooling, homogenization, and extraction of total nucleic acids, a real-time PCR was applied for the detection of a panel of tick-borne pathogens, while additional conventional PCRs combined with Sanger sequencing were applied for the detection of viruses and typing of Rickettsia and Borrelia species. At least one pathogen was detected in 60 of the 80 (75%) tick pools. Rickettsia spp. predominated, as it was detected in 63.75% of the pools (51/80; MIR 12.81%), followed by Borrelia spp. (35 pools (45%); MIR 8.79%), while Anaplasma phagocytophilum was detected in 2 pools (2.5%, MIR 0.5%). The ticks of six Rickettsia-positive pools were tested individually (from stored half-ticks); all sequences were identical to those of R. monacensis. Similarly, the ticks of six Borrelia-positive pools were tested individually, and it was shown that four belonged to the genospecies Borrelia garinii and two to Borrelia valaisiana. Phleboviruses were detected in 3 pools (3.75%; MIR 0.75%), with sequences clustering in the Ixovirus genus, while nairoviruses were detected in 7 pools (8.75%; MIR 1.76%), with one sequence clustering in the Orthonairovirus genus, and six clustering in the Norwavirus genus. Although a small number of ticks from only one area in Greece were tested, a variety of pathogens together with recently identified viruses were detected, prompting further studies in ticks and surveillance studies in humans. Full article

(This article belongs to the Special Issue Advances in Spotted Fever)

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28 pages, 2086 KiB

Open AccessEditor’s ChoiceReview

Beyond Tradition: Exploring Cutting-Edge Approaches for Accurate Diagnosis of Human Filariasis

by Damian Pietrzak, Julia Weronika Łuczak and Marcin Wiśniewski

Pathogens 2024, 13(6), 447; https://doi.org/10.3390/pathogens13060447 - 24 May 2024

Cited by 1 | Viewed by 1605

Abstract

Filariasis is recognised as a global public health threat, particularly in tropical and subtropical regions. It is caused by infection with a nematode parasite of the superfamily Filarioidea, including Wuchereria bancrofti, Brugia malayi, Onchocerca volvulus, and Onchocerca lupi. Three [...] Read more.

Filariasis is recognised as a global public health threat, particularly in tropical and subtropical regions. It is caused by infection with a nematode parasite of the superfamily Filarioidea, including Wuchereria bancrofti, Brugia malayi, Onchocerca volvulus, and Onchocerca lupi. Three main types of filariasis have been classified: lymphatic filariasis, subcutaneous filariasis, and serous cavity filariasis. The symptoms exhibited by individuals afflicted with filariasis are diverse and contingent upon several variables, including the species of parasite, the host’s health and immune response, and the stage of infection. While many classical parasitological techniques are considered indispensable tools for the diagnosis of parasitic infections in humans, alternative methods are being sought due to their limitations. Novel tests based on host–parasite interactions offer a rapid, simple, sensitive, and specific diagnostic tool in comparison to traditional parasitological methods. This article presents methods developed in the 21st century for the diagnosis of filariasis caused by invasion from W. bancrofti, B. malayi, O. volvulus, and O. lupi, as well as techniques that are currently in use. The development of modern diagnostic methods based on molecular biology constitutes a significant advancement in the fight against filariasis. Full article

(This article belongs to the Special Issue New Insights into Molecular Epidemiology and Diagnostics of Human Pathogens)

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13 pages, 261 KiB

Open AccessEditor’s ChoiceReview

Human Cytomegalovirus Infection and Neurocognitive and Neuropsychiatric Health

by Shawn D. Gale, Thomas J. Farrer, Reagan Erbstoesser, Scott MacLean and Dawson W. Hedges

Pathogens 2024, 13(5), 417; https://doi.org/10.3390/pathogens13050417 - 16 May 2024

Cited by 1 | Viewed by 2123

Abstract

A common infection, human cytomegalovirus (HCMV) has been associated with a variety of human diseases, including cardiovascular disease and possibly certain cancers. HCMV has also been associated with cognitive, psychiatric, and neurological conditions. Children with congenital or early-life HCMV are at risk for [...] Read more.

A common infection, human cytomegalovirus (HCMV) has been associated with a variety of human diseases, including cardiovascular disease and possibly certain cancers. HCMV has also been associated with cognitive, psychiatric, and neurological conditions. Children with congenital or early-life HCMV are at risk for microcephaly, cerebral palsy, and sensorineural hearing loss, although in many cases sensorineural loss may resolve. In addition, HCMV can be associated with neurodevelopmental impairment, which may improve with time. In young, middle-aged, and older adults, HCMV has been adversely associated with cognitive function in some but not in all studies. Research has linked HCMV to Alzheimer’s and vascular dementia, but again not all findings consistently support these associations. In addition, HCMV has been associated with depressive disorder, bipolar disorder, anxiety, and autism-spectrum disorder, although the available findings are likewise inconsistent. Given associations between HCMV and a variety of neurocognitive and neuropsychiatric disorders, additional research investigating reasons for the considerable inconsistencies in the currently available findings is needed. Additional meta-analyses and more longitudinal studies are needed as well. Research into the effects of antiviral medication on cognitive and neurological outcomes and continued efforts in vaccine development have potential to lower the neurocognitive, neuropsychiatric, and neurological burden of HCMV infection. Full article

(This article belongs to the Special Issue Understanding Human Cytomegalovirus Pathogenesis: Evidence from the Clinic and Laboratory Models)

15 pages, 5079 KiB

Open AccessEditor’s ChoiceArticle

Infectivity of Wild-Bird Origin Influenza A Viruses in Minnesota Wetlands across Seasons

by Rebecca L. Poulson, Andrew B. Reeves, Christina A. Ahlstrom, Laura C. Scott, Laura E. Hubbard, Alinde Fojtik, Deborah L. Carter, David E. Stallknecht and Andrew M. Ramey

Pathogens 2024, 13(5), 406; https://doi.org/10.3390/pathogens13050406 - 14 May 2024

Viewed by 1333

Abstract

The environmental tenacity of influenza A viruses (IAVs) in the environment likely plays a role in their transmission; IAVs are able to remain infectious in aquatic habitats and may have the capacity to seed outbreaks when susceptible wild bird hosts utilize these same [...] Read more.

The environmental tenacity of influenza A viruses (IAVs) in the environment likely plays a role in their transmission; IAVs are able to remain infectious in aquatic habitats and may have the capacity to seed outbreaks when susceptible wild bird hosts utilize these same environments months or even seasons later. Here, we aimed to assess the persistence of low-pathogenicity IAVs from naturally infected ducks in Northwestern Minnesota through a field experiment. Viral infectivity was measured using replicate samples maintained in distilled water in a laboratory setting as well as in filtered water from four natural water bodies maintained in steel perforated drums (hereafter, mesocosms) within the field from autumn 2020 to spring 2021. There was limited evidence for the extended persistence of IAVs held in mesocosms; from 65 initial IAV-positive samples, only six IAVs persisted to at least 202 days in the mesocosms compared to 17 viruses persisting at least this long when held under temperature-controlled laboratory settings in distilled water. When accounting for the initial titer of samples, viruses detected at a higher concentration at the initiation of the experiment persisted longer than those with a lower starting titer. A parallel experimental laboratory model was used to further explore the effects of water type on viral persistence, and the results supported the finding of reduced tenacity of IAVs held in mesocosms compared to distilled water. The results of this investigation provide evidence that many factors, including temperature and physicochemical properties, impact the duration of viral infectivity in natural settings, further extending our understanding of the potential and limitations of environmental-based methodologies to recover infectious IAVs. Full article

(This article belongs to the Special Issue Pathogenesis, Epidemiology, and Control of Animal Influenza Viruses)

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14 pages, 2428 KiB

Open AccessEditor’s ChoiceArticle

Neutrophils Expressing Programmed Death-Ligand 1 Play an Indispensable Role in Effective Bacterial Elimination and Resolving Inflammation in Methicillin-Resistant Staphylococcus aureus Infection

by Azusa Terasaki, Faizan Ahmed, Alato Okuno, Zhenzi Peng, Duo-Yao Cao and Suguru Saito

Pathogens 2024, 13(5), 401; https://doi.org/10.3390/pathogens13050401 - 11 May 2024

Cited by 1 | Viewed by 1545

Abstract

Programmed death ligand 1 (PD-L1) is a co-inhibitory molecule expressed on the surface of various cell types and known for its suppressive effect on T cells through its interaction with PD-1. Neutrophils also express PD-L1, and its expression is elevated in specific situations; [...] Read more.

Programmed death ligand 1 (PD-L1) is a co-inhibitory molecule expressed on the surface of various cell types and known for its suppressive effect on T cells through its interaction with PD-1. Neutrophils also express PD-L1, and its expression is elevated in specific situations; however, the immunobiological role of PD-L1⁺ neutrophils has not been fully characterized. Here, we report that PD-L1-expressing neutrophils increased in methicillin-resistant Staphylococcus aureus (MRSA) infection are highly functional in bacterial elimination and supporting inflammatory resolution. The frequency of PD-L1⁺ neutrophils was dramatically increased in MRSA-infected mice, and this population exhibited enhanced activity in bacterial elimination compared to PD-L1- neutrophils. The administration of PD-L1 monoclonal antibody did not impair PD-L1⁺ neutrophil function, suggesting that PD-L1 expression itself does not influence neutrophil activity. However, PD-1/PD-L1 blockade significantly delayed liver inflammation resolution in MRSA-infected mice, as indicated by their increased plasma alanine transaminase (ALT) levels and frequencies of inflammatory leukocytes in the liver, implying that neutrophil PD-L1 suppresses the inflammatory response of these cells during the acute phase of MRSA infection. Our results reveal that elevated PD-L1 expression can be a marker for the enhanced anti-bacterial function of neutrophils. Moreover, PD-L1⁺ neutrophils are an indispensable population attenuating inflammatory leukocyte activities, assisting in a smooth transition into the resolution phase in MRSA infection. Full article

(This article belongs to the Special Issue Current Research on Host–Pathogen Interaction in 2024)

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12 pages, 480 KiB

Open AccessEditor’s ChoiceArticle

Mycobacterium avium subsp. paratuberculosis in Wild Boar (Sus scrofa) in Portugal

by Ana Cristina Matos, Luis Figueira, Maria Helena Martins, Luís Cardoso, Manuela Matos, Maria de Lurdes Pinto and Ana Cláudia Coelho

Pathogens 2024, 13(5), 389; https://doi.org/10.3390/pathogens13050389 - 8 May 2024

Viewed by 1223

Abstract

Paratuberculosis, or Johne’s disease, caused by Mycobacterium avium subsp. paratuberculosis (MAP), is a chronic granulomatous enteritis affecting both domestic and wild ruminants. The agent was also found in wild mammals such as wild boar (Sus scrofa); however, the role of wild [...] Read more.

Paratuberculosis, or Johne’s disease, caused by Mycobacterium avium subsp. paratuberculosis (MAP), is a chronic granulomatous enteritis affecting both domestic and wild ruminants. The agent was also found in wild mammals such as wild boar (Sus scrofa); however, the role of wild mammals in the epidemiology of MAP is unclear. During the research period, 941 free-ranging wild boar (S. scrofa) legally hunted in two locations in the central–eastern region of Portugal were examined. Ninety-seven wild boars exhibited one or more gross lesions and were tested for the presence of Mycobacterium avium subsp. paratuberculosis using acid-fast staining, mycobacterial culture, polymerase chain reaction (PCR), and histopathological examination. Forty-five animals (46.4%, 95% CI: 36.5–56.3%) were identified as infected, as indicated by positive results in culture and/or PCR. The findings revealed that the most significant risk factor was being a juvenile compared to yearlings and adults (OR = 10.2, 95% CI: 2.2–48.0). Based on our results, 37.9% (n = 11) of the infected animals were considered suitable for human consumption. Our findings offer novel insights into mycobacterial infections in wild boar populations in Portugal and suggest that wild boar could be a source of human infection if zoonotic potential is considered. Full article

(This article belongs to the Special Issue Wildlife Hosts Pathogen Interaction)

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14 pages, 967 KiB

Open AccessEditor’s ChoiceArticle

Clinical and Diagnostic Features of West Nile Virus Neuroinvasive Disease in New York City

by Jackson A. Roberts, Carla Y. Kim, Amy Dean, Karen E. Kulas, Kirsten St. George, Hai E. Hoang and Kiran T. Thakur

Pathogens 2024, 13(5), 382; https://doi.org/10.3390/pathogens13050382 - 3 May 2024

Cited by 2 | Viewed by 2185

Abstract

West Nile virus (WNV) neuroinvasive disease (WNND) occurs in approximately 1 percent of WNV-infected patients and typically presents as encephalitis, meningitis, or acute flaccid paralysis (AFP). WNND remains a difficult inpatient diagnosis, creating significant challenges for prognostication and therapy selection. We characterized the [...] Read more.

West Nile virus (WNV) neuroinvasive disease (WNND) occurs in approximately 1 percent of WNV-infected patients and typically presents as encephalitis, meningitis, or acute flaccid paralysis (AFP). WNND remains a difficult inpatient diagnosis, creating significant challenges for prognostication and therapy selection. We characterized the clinical and diagnostic features of WNND cases at two major academic medical centers in New York City in routine clinical practice. We retrospectively reviewed the charts of thirty-six patients with WNND, including twenty-six encephalitis, four meningitis, and six AFP cases. The most common presenting symptoms were fever (86.1%) and gastrointestinal symptoms (38.9%) in addition to altered mental status (72.2%), lethargy (63.9%), gait disturbances (46.2%), and headache (44.4%). Fourteen (48.3%) patients displayed acute magnetic resonance imaging (MRI) findings, particularly T2 hyperintensities in the bilateral thalami, brainstem, and deep white matter. New York State Department of Health WNV CSF IgM testing was utilized for diagnosis in 58.3% of patients; however, just 38.1% had the result by discharge, compared to 85.6% of those who underwent serum IgM testing. The median length of stay was 13.5 days, 38.9% were intubated, and three patients (8.9%) died during acute hospitalization. Our findings underscore the morbidity, mortality, and diagnostic challenges of WNND, suggesting the potential utility of serum IgM testing in combination with confirmatory CSF testing to expedite diagnosis in the acute setting. Full article

(This article belongs to the Special Issue Viral Infections of Humans: Epidemiology and Control)

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12 pages, 3806 KiB

Open AccessEditor’s ChoiceArticle

Novel Genotype of HA Clade 2.3.4.4b H5N8 Subtype High Pathogenicity Avian Influenza Virus Emerged at a Wintering Site of Migratory Birds in Japan, 2021/22 Winter

by Berihun Dires Mihiretu, Tatsufumi Usui, Masahiro Kiyama, Kosuke Soda and Tsuyoshi Yamaguchi

Pathogens 2024, 13(5), 380; https://doi.org/10.3390/pathogens13050380 - 2 May 2024

Viewed by 2371

Abstract

Surveillance of avian influenza virus (AIV) was conducted in the 2021–2022 winter season at a wintering site of migratory Anatidae in Japan. An H5N8 subtype high pathogenicity AIV (HPAIV) with a unique gene constellation and four low pathogenicity AIVs (LPAIVs) were isolated from [...] Read more.

Surveillance of avian influenza virus (AIV) was conducted in the 2021–2022 winter season at a wintering site of migratory Anatidae in Japan. An H5N8 subtype high pathogenicity AIV (HPAIV) with a unique gene constellation and four low pathogenicity AIVs (LPAIVs) were isolated from environmental samples. The genetic origin of the HPAIV (NK1201) was determined with whole-genome sequencing and phylogenetic analyses. Six of NK1201’s eight genes were closely related to HA clade 2.3.4.4b H5N8 subtype HPAIVs, belonging to the G2a group, which was responsible for outbreaks in poultry farms in November 2021 in Japan. However, the remaining two genes, PB1 and NP, most closely matched those of the LPAIVs H7N7 and H1N8, which were isolated at the same place in the same 2021–2022 winter. No virus of the NK1201 genotype had been detected prior to the 2021–2022 winter, indicating that it emerged via genetic reassortment among HPAIV and LPAIVs, which were prevalent at the same wintering site. In addition, experimental infection in chickens indicated that NK1201 had slightly different infectivity compared to the reported infectivity of the representative G2a group H5N8 HPAIV, suggesting that the PB1 and NP genes derived from LPAIVs might have affected the pathogenicity of the virus in chickens. Our results directly demonstrate the emergence of a novel genotype of H5N8 HPAIV through gene reassortment at a wintering site. Analyses of AIVs at wintering sites can help to identify the emergence of novel HPAIVs, which pose risks to poultry, livestock, and humans. Full article

(This article belongs to the Special Issue Pathogens of Wild Birds: Prevalence, Molecular and Morphological Characterization)

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9 pages, 468 KiB

Open AccessEditor’s ChoiceArticle

Post-Conization HPV Vaccination and Its Impact on Viral Status: A Retrospective Cohort Study in Troms and Finnmark, 2022

by Marie Rykkelid, Helga Marie Wennberg, Elin Richardsen and Sveinung Wergeland Sørbye

Pathogens 2024, 13(5), 381; https://doi.org/10.3390/pathogens13050381 - 2 May 2024

Viewed by 2194

Abstract

Human papillomavirus (HPV) is associated with cellular changes in the cervix leading to cancer, which highlights the importance of vaccination in preventing HPV infections and subsequent cellular changes. Women undergoing the loop electrosurgical excision procedure (LEEP), a treatment for high-grade cervical intraepithelial neoplasia [...] Read more.

Human papillomavirus (HPV) is associated with cellular changes in the cervix leading to cancer, which highlights the importance of vaccination in preventing HPV infections and subsequent cellular changes. Women undergoing the loop electrosurgical excision procedure (LEEP), a treatment for high-grade cervical intraepithelial neoplasia (CIN2+), remain at risk of recurrence. This study assessed the effect of post-conization HPV vaccination on the viral status of women at six months post-conization, aiming to evaluate the vaccine’s effectiveness in preventing recurrence of CIN2+. A retrospective cohort study was conducted among women in Troms and Finnmark who underwent conization in 2022. Using the SymPathy database and the national vaccination register (SYSVAK), we analyzed the vaccination statuses and HPV test results of women born before 1991, who had not received the HPV vaccine prior to conization. Out of 419 women undergoing conization, 243 met the inclusion criteria. A significant association was found between post-conization HPV vaccination and a negative HPV test at six months of follow-up (ARR = 12.1%, p = 0.039). Post-conization HPV vaccination significantly reduced the risk of a positive HPV test at the first follow-up, suggesting its potential in preventing the recurrence of high-grade cellular changes. However, the retrospective design and the insufficient control of confounding variables in this study underscore the need for further studies to confirm these findings. Full article

(This article belongs to the Special Issue Viral Infections of Humans: Epidemiology and Control)

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9 pages, 600 KiB

Open AccessEditor’s ChoiceArticle

Seroprevalence of Toxoplasma gondii among HIV Positive Patients under Surveillance in Greek Infectious Disease Units: A Screening Study with Comparative Evaluation of Serological Methods

by Chrysa Voyiatzaki, Apollon Dareios Zare Chormizi, Maria E. Tsoumani, Antonia Efstathiou, Konstantinos Konstantinidis, Dimitrios Chaniotis, Georgios Chrysos, Aikaterini Argyraki, Vasileios Papastamopoulos and Marika Kotsianopoulou

Pathogens 2024, 13(5), 375; https://doi.org/10.3390/pathogens13050375 - 30 Apr 2024

Cited by 1 | Viewed by 2050

Abstract

This study aims to screen for IgG antibodies against Toxoplasma gondii (T. gondii) in the sera of 155 newly diagnosed Human Immunodeficiency Virus (HIV) positive patients under surveillance in Greek Infectious Disease Units. Additionally, risk factors based on patient demographics were [...] Read more.

This study aims to screen for IgG antibodies against Toxoplasma gondii (T. gondii) in the sera of 155 newly diagnosed Human Immunodeficiency Virus (HIV) positive patients under surveillance in Greek Infectious Disease Units. Additionally, risk factors based on patient demographics were examined, and a comparative evaluation of commercially available serological methods was conducted. Three methods were employed to detect IgG antibodies against T. gondii: Enzyme-Linked Immunosorbent Assay (ELISA), Indirect Immunofluorescence Antibody Test (IFAT), and Western Blot (WB), which was used as a reference here. Forty-nine sera samples were true-positive for IgG antibodies against T. gondii, resulting in a 31.61% positivity rate, and the immunoassay test statistical reliability analysis resulted in higher IFAT accuracy (90.97%) compared to ELISA (76.26%). Furthermore, statistical analysis of demographic and immunological data included in the study placed female and foreign/non-Greek individuals at 2.24 (p = 0.0009) and 2.34 (p = 0.0006) times higher risk of positive T. gondii IgG testing compared to their male and Greek counterparts, respectively. Our findings on positivity rates and comparative serology underscore the importance of early and suitable screening measures for newly diagnosed HIV+ patients to mitigate the life-threatening outcomes that may arise from a potential subsequent T. gondii activation. Full article

(This article belongs to the Special Issue One Health: New Approaches, Research and Innovation to Zoonoses)

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22 pages, 5093 KiB

Open AccessEditor’s ChoiceArticle

Cognitive Effects of Toxoplasma and CMV Infections: A Cross-Sectional Study of 557 Young Adults Considering Modulation by Sex and Rh Factor

by Jaroslav Flegr, Veronika Chvátalová, Lenka Příplatová, Petr Tureček, Petr Kodym, Blanka Šebánková and Šárka Kaňková

Pathogens 2024, 13(5), 363; https://doi.org/10.3390/pathogens13050363 - 28 Apr 2024

Cited by 1 | Viewed by 4485

Abstract

One-third of humanity harbors a lifelong infection with Toxoplasma gondii, and probably about 80% are infected with human cytomegalovirus (CMV). This study aims to delineate the associations between toxoplasmosis and cognitive abilities and compare these to the associations with CMV. We evaluated [...] Read more.

One-third of humanity harbors a lifelong infection with Toxoplasma gondii, and probably about 80% are infected with human cytomegalovirus (CMV). This study aims to delineate the associations between toxoplasmosis and cognitive abilities and compare these to the associations with CMV. We evaluated the cognitive performance of 557 students, who had been examined for Toxoplasma and CMV infections, using intelligence, memory, and psychomotor tests. The results indicated cognitive impairments in seropositive individuals for both pathogens, with variations in cognitive impact related to sex and the Rh factor. Specifically, Toxoplasma infection was associated with lower IQ in men, whereas CMV was predominantly associated with worse performance by women when testing memory and reaction speeds. Analysis of the antibody concentrations indicated that certain Toxoplasma-associated cognitive detrimental effects may wane (impaired intelligence) or worsen (impaired reaction times) over time following infection. The findings imply that the cognitive impairments caused by both neurotropic pathogens are likely due to pathological changes in the brain rather than from direct manipulative action by the parasites. Full article

(This article belongs to the Section Parasitic Pathogens)

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14 pages, 1152 KiB

Open AccessEditor’s ChoiceReview

The Role of Prevotella Species in Female Genital Tract Infections

by Sheridan D. George, Olivia T. Van Gerwen, Chaoling Dong, Lúcia G. V. Sousa, Nuno Cerca, Jacob H. Elnaggar, Christopher M. Taylor and Christina A. Muzny

Pathogens 2024, 13(5), 364; https://doi.org/10.3390/pathogens13050364 - 28 Apr 2024

Viewed by 3935

Abstract

Female genital tract infections (FGTIs) include vaginal infections (e.g., bacterial vaginosis [BV]), endometritis, pelvic inflammatory disease [PID], and chorioamnionitis [amniotic fluid infection]. They commonly occur in women of reproductive age and are strongly associated with multiple adverse health outcomes including increased risk of [...] Read more.

Female genital tract infections (FGTIs) include vaginal infections (e.g., bacterial vaginosis [BV]), endometritis, pelvic inflammatory disease [PID], and chorioamnionitis [amniotic fluid infection]. They commonly occur in women of reproductive age and are strongly associated with multiple adverse health outcomes including increased risk of HIV/sexually transmitted infection acquisition and transmission, infertility, and adverse birth outcomes such as preterm birth. These FGTIs are characterized by a disruption of the cervicovaginal microbiota which largely affects host immunity through the loss of protective, lactic acid-producing Lactobacillus spp. and the overgrowth of facultative and strict anaerobic bacteria. Prevotella species (spp.), anaerobic Gram-negative rods, are implicated in the pathogenesis of multiple bacterial FGTIs. Specifically, P. bivia, P. amnii, and P. timonensis have unique virulence factors in this setting, including resistance to antibiotics commonly used in treatment. Additionally, evidence suggests that the presence of Prevotella spp. in untreated BV cases can lead to infections of the upper female genital tract by ascension into the uterus. This narrative review aims to explore the most common Prevotella spp. in FGTIs, highlight their important role in the pathogenesis of FGTIs, and propose future research in this area. Full article

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20 pages, 1888 KiB

Open AccessEditor’s ChoiceReview

Hepatitis Delta Virus and Hepatocellular Carcinoma

by Daniele Lombardo, Maria Stella Franzè, Giuseppe Caminiti and Teresa Pollicino

Pathogens 2024, 13(5), 362; https://doi.org/10.3390/pathogens13050362 - 27 Apr 2024

Cited by 1 | Viewed by 1731

Abstract

The hepatitis D virus (HDV) is a compact, enveloped, circular RNA virus that relies on hepatitis B virus (HBV) envelope proteins to initiate a primary infection in hepatocytes, assemble, and secrete new virions. Globally, HDV infection affects an estimated 12 million to 72 [...] Read more.

The hepatitis D virus (HDV) is a compact, enveloped, circular RNA virus that relies on hepatitis B virus (HBV) envelope proteins to initiate a primary infection in hepatocytes, assemble, and secrete new virions. Globally, HDV infection affects an estimated 12 million to 72 million people, carrying a significantly elevated risk of developing cirrhosis, liver failure, and hepatocellular carcinoma (HCC) compared to an HBV mono-infection. Furthermore, HDV-associated HCC often manifests at a younger age and exhibits more aggressive characteristics. The intricate mechanisms driving the synergistic carcinogenicity of the HDV and HBV are not fully elucidated but are believed to involve chronic inflammation, immune dysregulation, and the direct oncogenic effects of the HDV. Indeed, recent data highlight that the molecular profile of HCC associated with HDV is unique and distinct from that of HBV-induced HCC. However, the question of whether the HDV is an oncogenic virus remains unanswered. In this review, we comprehensively examined several crucial aspects of the HDV, encompassing its epidemiology, molecular biology, immunology, and the associated risks of liver disease progression and HCC development. Full article

(This article belongs to the Special Issue Oncoviruses and Molecular Mechanisms of Viral Carcinogenesis)

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11 pages, 1569 KiB

Open AccessEditor’s ChoiceReview

Therapeutic Applications of Aggregatibacter actinomycetemcomitans Leukotoxin

by Scott C. Kachlany and Brian A. Vega

Pathogens 2024, 13(5), 354; https://doi.org/10.3390/pathogens13050354 - 25 Apr 2024

Cited by 1 | Viewed by 1627

Abstract

Aggregatibacter actinomycetemcomitans is a Gram-negative oral bacterium that has been primarily studied for its role in causing periodontal disease. The bacterium has also been implicated in several systemic diseases such as endocarditis and soft tissue abscesses. Leukotoxin (LtxA) is perhaps the best studied [...] Read more.

Aggregatibacter actinomycetemcomitans is a Gram-negative oral bacterium that has been primarily studied for its role in causing periodontal disease. The bacterium has also been implicated in several systemic diseases such as endocarditis and soft tissue abscesses. Leukotoxin (LtxA) is perhaps the best studied protein virulence factor from A. actinomycetemcomitans. The protein can rapidly destroy white blood cells (WBCs), helping the bacterium to subvert the host immune system. The functional receptor for LtxA is lymphocyte function associated antigen-1 (LFA-1), which is expressed exclusively on the surfaces of WBCs. Bacterial expression and secretion of the protein are highly regulated and controlled by a number of genetic and environmental factors. The mechanism of LtxA action on WBCs varies depending on the type of cell that is being killed, and the protein has been shown to activate numerous cell death pathways in susceptible cells. In addition to serving as an important virulence factor for the bacterium, because of its exquisite specificity and rapid activity, LtxA is also being investigated as a therapeutic agent that may be used to treat diseases such as hematological malignancies and autoimmune/inflammatory diseases. It is our hope that this review will inspire an increased intensity of research related to LtxA and its effect on Aggressive Periodontitis, the disease that led to its initial discovery. Full article

(This article belongs to the Special Issue Aggregatibacter actinomycetemcomitans)

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13 pages, 412 KiB

Open AccessEditor’s ChoiceReview

Group A Streptococcal Infections in Pediatric Age: Updates about a Re-Emerging Pathogen

by Giada Maria Di Pietro, Paola Marchisio, Pietro Bosi, Massimo Luca Castellazzi and Paul Lemieux

Pathogens 2024, 13(5), 350; https://doi.org/10.3390/pathogens13050350 - 24 Apr 2024

Cited by 1 | Viewed by 2307

Abstract

Group A Streptococcus (GAS) presents a significant global health burden due to its diverse clinical manifestations ranging from mild infections to life-threatening invasive diseases. While historically stable, the incidence of GAS infections declined during the COVID-19 pandemic but resurged following the relaxation of [...] Read more.

Group A Streptococcus (GAS) presents a significant global health burden due to its diverse clinical manifestations ranging from mild infections to life-threatening invasive diseases. While historically stable, the incidence of GAS infections declined during the COVID-19 pandemic but resurged following the relaxation of preventive measures. Despite general responsiveness to β-lactam antibiotics, there remains an urgent need for a GAS vaccine due to its substantial global disease burden, particularly in low-resource settings. Vaccine development faces numerous challenges, including the extensive strain diversity, the lack of suitable animal models for testing, potential autoimmune complications, and the need for global distribution, while addressing socioeconomic disparities in vaccine access. Several vaccine candidates are in various stages of development, offering hope for effective prevention strategies in the future. Full article

(This article belongs to the Special Issue Emerging and Re-emerging Infections in Pediatrics)

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20 pages, 1913 KiB

Open AccessEditor’s ChoiceReview

Co-Infections and Superinfections between HIV-1 and Other Human Viruses at the Cellular Level

by Chiara Acchioni, Silvia Sandini, Marta Acchioni and Marco Sgarbanti

Pathogens 2024, 13(5), 349; https://doi.org/10.3390/pathogens13050349 - 24 Apr 2024

Viewed by 2221

Abstract

Co-infection or superinfection of the host by two or more virus species is a common event, potentially leading to viral interference, viral synergy, or neutral interaction. The simultaneous presence of two or more viruses, even distantly related, within the same cell depends upon [...] Read more.

Co-infection or superinfection of the host by two or more virus species is a common event, potentially leading to viral interference, viral synergy, or neutral interaction. The simultaneous presence of two or more viruses, even distantly related, within the same cell depends upon viral tropism, i.e., the entry of viruses via receptors present on the same cell type. Subsequently, productive infection depends on the ability of these viruses to replicate efficiently in the same cellular environment. HIV-1 initially targets CCR5-expressing tissue memory CD4⁺ T cells, and in the absence of early cART initiation, a co-receptor switch may occur, leading to the infection of naïve and memory CXCR4-expressing CD4⁺ T cells. HIV-1 infection of macrophages at the G₁ stage of their cell cycle also occurs in vivo, broadening the possible occurrence of co-infections between HIV-1 and other viruses at the cellular level. Moreover, HIV-1-infected DCs can transfer the virus to CD4⁺ T cells via trans-infection. This review focuses on the description of reported co-infections within the same cell between HIV-1 and other human pathogenic, non-pathogenic, or low-pathogenic viruses, including HIV-2, HTLV, HSV, HHV-6/-7, GBV-C, Dengue, and Ebola viruses, also discussing the possible reciprocal interactions in terms of virus replication and virus pseudotyping. Full article

(This article belongs to the Special Issue Editorial Board Members’ Collection Series: HIV and Viral Co-infections)

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12 pages, 1729 KiB

Open AccessEditor’s ChoiceArticle

Trends in Non-Tuberculous Mycobacterial Lung Disease and Treatment Outcomes in a Low-Tuberculosis Prevalence Setting: A Retrospective Analysis

by Biplob Kumar Mohanty, Tomas Mikal Lind Eagan, Bernt Bøgvald Aarli, Dag Harald Skutlaberg and Tehmina Mustafa

Pathogens 2024, 13(4), 344; https://doi.org/10.3390/pathogens13040344 - 22 Apr 2024

Viewed by 1510

Abstract

Background: Information on the management of non-tuberculous mycobacterial (NTM) lung infection and disease is scarce. The aim of this study was to investigate the trends in NTM lung infections, and the factors associated with the initiation of treatment and treatment outcomes. Methods: A [...] Read more.

Background: Information on the management of non-tuberculous mycobacterial (NTM) lung infection and disease is scarce. The aim of this study was to investigate the trends in NTM lung infections, and the factors associated with the initiation of treatment and treatment outcomes. Methods: A retrospective analysis was carried out on patient medical records from Haukeland University Hospital, Bergen, Norway, from 2000 to 2021. Results: Among 154 patients with NTM lung infection, the majority (70%) were older than 65 years, and 49% had an underlying pulmonary comorbidity. The most frequently observed mycobacterial species was M. avium complex (MAC), followed by M. malmoense and M. abscessus. In total, 72 (47%) patients received antibiotic treatment. Patients with high symptom scores, aged below 65, and with MAC infection had more than three times the odds of receiving antibiotic treatment. A favourable response and culture conversion was observed in 53 of 72 (74%) patients. However, 17 (32%) of them had a relapse. Out of 82 patients who did not receive treatment, 45 (55%) had spontaneous culture conversion, and 8 (18%) of them had a relapse. No factor was identified to be significantly associated with a favourable treatment response. Conclusion: A favourable response to treatment was seen in 74% of patients with a high relapse rate. Full article

(This article belongs to the Section Epidemiology of Infectious Diseases)

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30 pages, 7697 KiB

Open AccessEditor’s ChoiceArticle

Isospora and Lankesterella Parasites (Eimeriidae, Apicomplexa) of Passeriform Birds in Europe: Infection Rates, Phylogeny, and Pathogenicity

by Carina Keckeisen, Alžbeta Šujanová, Tanja Himmel, Julia Matt, Nora Nedorost, Carolina R. F. Chagas, Herbert Weissenböck and Josef Harl

Pathogens 2024, 13(4), 337; https://doi.org/10.3390/pathogens13040337 - 18 Apr 2024

Viewed by 2083

Abstract

Wild birds are common hosts to numerous intracellular parasites such as single-celled eukaryotes of the family Eimeriidae (order Eucoccidiorida, phylum Apicomplexa). We investigated the infection rates, phylogeny, and pathogenicity of Isospora and Lankesterella parasites in wild and captive passerine birds. Blood and tissue [...] Read more.

Wild birds are common hosts to numerous intracellular parasites such as single-celled eukaryotes of the family Eimeriidae (order Eucoccidiorida, phylum Apicomplexa). We investigated the infection rates, phylogeny, and pathogenicity of Isospora and Lankesterella parasites in wild and captive passerine birds. Blood and tissue samples of 815 wild and 15 deceased captive birds from Europe were tested using polymerase chain reaction and partial sequencing of the mitochondrial cytochrome b and cytochrome c oxidase I and the nuclear 18S rRNA gene. The infection rate for Lankesterella in wild birds was 10.7% compared to 5.8% for Isospora. Chromogenic in situ hybridization with probes targeting the parasites’ 18S rRNA was employed to identify the parasites’ presence in multiple organs, and hematoxylin–eosin staining was performed to visualize the parasite stages and assess associated lesions. Isospora parasites were mainly identified in the intestine, spleen, and liver. Extraintestinal tissue stages of Isospora were accompanied by predominantly lymphohistiocytic inflammation of varying severity. Lankesterella was most frequently detected in the spleen, lung, and brain; however, infected birds presented only a low parasite burden without associated pathological changes. These findings contribute to our understanding of Isospora and Lankesterella parasites in wild birds. Full article

(This article belongs to the Collection Pathology and Parasitic Diseases of Animals)

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10 pages, 217 KiB

Open AccessEditor’s ChoiceArticle

Development of a Targeted NGS Assay for the Detection of Respiratory Pathogens including SARS-CoV-2 in Felines

by Jobin J. Kattoor, Mothomang Mlalazi-Oyinloye, Sarah M. Nemser and Rebecca P. Wilkes

Pathogens 2024, 13(4), 335; https://doi.org/10.3390/pathogens13040335 - 17 Apr 2024

Cited by 1 | Viewed by 2093

Abstract

Acute respiratory diseases in felines can be attributed to a diverse range of pathogens. The recent emergence of novel viruses, particularly SARS-CoV-2 and its variants, has also been associated with respiratory ailments in cats and other pets, underscoring the need for a highly [...] Read more.

Acute respiratory diseases in felines can be attributed to a diverse range of pathogens. The recent emergence of novel viruses, particularly SARS-CoV-2 and its variants, has also been associated with respiratory ailments in cats and other pets, underscoring the need for a highly sensitive diagnostic assay capable of concurrently detecting multiple respiratory pathogens. In this study, we developed a targeted next generation sequencing panel using Ion Torrent Ampliseq technology to detect multiple respiratory pathogens, including recent SARS-CoV-2 variants and Feline herpesvirus-1, Feline calicivirus, Bordetella bronchiseptica, Mycoplasmopsis (previously Mycoplasma) felis, and Chlamydia felis. A PCR amplification-based library preparation, employing primers designed for pathogen target regions, was synthesized and divided into two pools, followed by sequencing and assembly to a repertoire of target pathogen genomes. Analytical sensitivity was assessed based on Ct values from real-time PCR for the corresponding pathogens, indicating an equivalent detection limit. Most of the pathogens under study were positively identified to a limit of approximately Ct 36, whereas for Feline herpesvirus-1 and SARS-CoV-2, positive reads were observed in samples with a Ct of 37. Based on a limited number of samples, the diagnostic sensitivity values for the SARS-CoV-2, Feline herpesvirus-1, and M. felis samples were 100% with no false negative results. The diagnostic specificity of SARS-CoV-2, Feline herpesvirus-1, Feline calicivirus, and C. felis were 100%. Importantly, none of the target primers exhibited non-specific amplification, ensuring the absence of false positive results for other pathogens within the study. Additionally, the assay’s specificity was validated by cross-referencing the raw sequencing data with established databases like BLAST, affirming the high specificity of the targeted Next-Generation Sequencing (tNGS) assay. Variations in the sequencing reads of different pathogens were observed when subjected to diverse extraction methods. Rigorous assessment of the assay’s reliability involved reproducibility across testing personnel and repeated runs. The developed assay’s clinical applicability was tested using samples submitted to the diagnostic laboratory from cat shelters and suspected cases. The developed targeted next-generation sequencing methodology empowers the detection of multiple respiratory pathogens manifesting similar clinical symptoms while offering confirmation of results through genome sequencing. Full article

(This article belongs to the Special Issue Diagnostics of Animal Viral Infectious Diseases)

15 pages, 1318 KiB

Open AccessEditor’s ChoiceReview

Dengue-Associated Hemophagocytic Lymphohistiocytosis: A Narrative Review of Its Identification and Treatment

by Kay Choong See

Pathogens 2024, 13(4), 332; https://doi.org/10.3390/pathogens13040332 - 17 Apr 2024

Cited by 2 | Viewed by 3526

Abstract

Dengue’s lack of specific treatments beyond supportive care prompts a focus on uncovering additional pathophysiological factors. Dengue-associated hemophagocytic lymphohistiocytosis (HLH), characterized by dysregulated macrophage activation and cytokine storm, remains underexplored despite its potential to worsen disease severity and mortality. While rare, dengue-associated HLH [...] Read more.

Dengue’s lack of specific treatments beyond supportive care prompts a focus on uncovering additional pathophysiological factors. Dengue-associated hemophagocytic lymphohistiocytosis (HLH), characterized by dysregulated macrophage activation and cytokine storm, remains underexplored despite its potential to worsen disease severity and mortality. While rare, dengue-associated HLH disproportionately affects severe cases, significantly impacting mortality rates. To mitigate high mortality, early identification and familiarity with dengue-associated HLH are imperative for prompt treatment by clinicians. This narrative review therefore aims to examine the current clinical and therapeutic knowledge on dengue-associated HLH, and act as a resource for clinicians to improve their management of HLH associated with severe dengue. Dengue-associated HLH should be considered for all cases of severe dengue and may be suspected based on the presence of prolonged or recurrent fever for >7 days, or anemia without intravascular hemolysis or massive bleeding. Diagnosis relies on fulfilling at least five of the eight HLH-2004 criteria. Treatment predominantly involves short courses (3–4 days) of high-dose steroids (e.g., dexamethasone 10 mg/m²), with additional therapies considered in more severe presentations. Notably, outcomes can be favorable with steroid therapy alone. Full article

(This article belongs to the Special Issue Impact of Bacterial and Viral Pathogens on Sepsis Prevalence and Outcome)

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12 pages, 859 KiB

Open AccessEditor’s ChoiceArticle

Hepatitis C Prevalence and Birth Outcomes among Pregnant Women in the United States: A 2010–2020 Population Study

by Paul Wasuwanich, Songyos Rajborirug, Robert S. Egerman, Tony S. Wen and Wikrom Karnsakul

Pathogens 2024, 13(4), 321; https://doi.org/10.3390/pathogens13040321 - 14 Apr 2024

Viewed by 1527

Abstract

Background: The rates of hepatitis C virus (HCV) infection have increased in the pregnant population. We aim to describe the age-stratified clinical outcomes and trends for inpatient pregnant women with HCV in the U.S. Methods: We utilized hospitalization data from the 2010–2020 National [...] Read more.

Background: The rates of hepatitis C virus (HCV) infection have increased in the pregnant population. We aim to describe the age-stratified clinical outcomes and trends for inpatient pregnant women with HCV in the U.S. Methods: We utilized hospitalization data from the 2010–2020 National Inpatient Sample. Pregnancy and HCV were identified according to their ICD-9/ICD-10 codes. Demographic and clinical data including cirrhosis, mortality, preterm birth, and stillbirth were extracted. The age groups were defined as ≤18, 19–25, 26–34, and ≥35 years. Results: We identified 195,852 inpatient pregnant women with HCV, among whom 0.7% were ≤18, 26.7% were 19–25, 57.9% were 26–34, and 14.8% were ≥35 years of age. The hospitalization rates of pregnant women with HCV increased overall between 2010 and 2020, with the highest velocity in the 26–34 age group. The 26–34 age group had the highest HCV burden, with an age-standardized hospitalization rate of 660 per 100,000 in 2020. The rates of mortality and cirrhosis were significantly higher in the HCV cohort and increased further with age (p < 0.05). Among the HCV pregnant cohort, 151,017 (77.1%) delivered during hospitalization. Preterm births and stillbirths were significantly higher in the HCV pregnant cohort compared to the controls across multiple age groups (p < 0.05). Minority race/ethnicity was associated with increased mortality, cirrhosis, preterm birth, and stillbirth (p < 0.001). HIV co-infection, hepatitis B co-infection, and diabetes increased the odds of cirrhosis (p < 0.001). Conclusions: Hospitalizations of pregnant women with HCV are escalating, and these women are at increased risk of mortality, cirrhosis, preterm birth, and stillbirth with modifying factors, exacerbating risks further. Full article

(This article belongs to the Section Viral Pathogens)

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52 pages, 1537 KiB

Open AccessEditor’s ChoiceReview

Emerging Approaches for Mitigating Biofilm-Formation-Associated Infections in Farm, Wild, and Companion Animals

by Daniela Araújo, Ana Rita Silva, Rúben Fernandes, Patrícia Serra, Maria Margarida Barros, Ana Maria Campos, Ricardo Oliveira, Sónia Silva, Carina Almeida and Joana Castro

Pathogens 2024, 13(4), 320; https://doi.org/10.3390/pathogens13040320 - 13 Apr 2024

Cited by 4 | Viewed by 3107

Abstract

The importance of addressing the problem of biofilms in farm, wild, and companion animals lies in their pervasive impact on animal health and welfare. Biofilms, as resilient communities of microorganisms, pose a persistent challenge in causing infections and complicating treatment strategies. Recognizing and [...] Read more.

The importance of addressing the problem of biofilms in farm, wild, and companion animals lies in their pervasive impact on animal health and welfare. Biofilms, as resilient communities of microorganisms, pose a persistent challenge in causing infections and complicating treatment strategies. Recognizing and understanding the importance of mitigating biofilm formation is critical to ensuring the welfare of animals in a variety of settings, from farms to the wild and companion animals. Effectively addressing this issue not only improves the overall health of individual animals, but also contributes to the broader goals of sustainable agriculture, wildlife conservation, and responsible pet ownership. This review examines the current understanding of biofilm formation in animal diseases and elucidates the complex processes involved. Recognizing the limitations of traditional antibiotic treatments, mechanisms of resistance associated with biofilms are explored. The focus is on alternative therapeutic strategies to control biofilm, with illuminating case studies providing valuable context and practical insights. In conclusion, the review highlights the importance of exploring emerging approaches to mitigate biofilm formation in animals. It consolidates existing knowledge, highlights gaps in understanding, and encourages further research to address this critical facet of animal health. The comprehensive perspective provided by this review serves as a foundation for future investigations and interventions to improve the management of biofilm-associated infections in diverse animal populations. Full article

(This article belongs to the Special Issue Innovative Strategies to Counteract Microbial Biofilm Growth)

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18 pages, 288 KiB

Open AccessEditor’s ChoiceArticle

Analysis of Mycotoxins and Cytotoxicity of Airborne Molds Isolated from the Zoological Garden—Screening Research

by Kinga Plewa-Tutaj, Magdalena Twarużek, Robert Kosicki and Ewelina Soszczyńska

Pathogens 2024, 13(4), 294; https://doi.org/10.3390/pathogens13040294 - 30 Mar 2024

Cited by 1 | Viewed by 1741

Abstract

Objective: The objective of this paper was to assess the airborne mold contamination, secondary metabolite profiles, and cytotoxicity of the dominant fungal species isolated from the air in selected rooms at a Zoological Garden. Materials and methods: Fungal concentrations were measured with MAS-100 [...] Read more.

Objective: The objective of this paper was to assess the airborne mold contamination, secondary metabolite profiles, and cytotoxicity of the dominant fungal species isolated from the air in selected rooms at a Zoological Garden. Materials and methods: Fungal concentrations were measured with MAS-100 air samplers. The collected airborne fungi were identified using a combination of morphological and molecular methods. The cytotoxicity of 84 strains belonging to two Penicillium and Aspergillus genera was determined using the quantitative colorimetric MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium salt) assay. The mycotoxins were detected using high-performance liquid chromatography (HPLC) with a mass spectrometry detector. Results: The ITS gene was amplified and sequenced to identify the 132 species. For mycotoxicological and cytotoxicity analyses, 52 Penicillium isolates and 32 Aspergillus representatives were selected. Cytotoxicity was confirmed in 97.6% of cases analyzed. Using the LC-MS/MS method, 42 out of 84 strains produced at least one of the following toxins: ochratoxin A, ochratoxin B, patulin, gliotoxin, roquefortine C, griseofulvin, sterigmatocystin, fumonisin B2, moniliformin, and mycophenolic acid. Conclusions: Analytical methods for assessing the presence of mycotoxins in fungal isolates collected directly from the air have proven to be an effective tool. Our research provides new information on the occurrence of potentially toxin-producing molds within a zoo. Full article

(This article belongs to the Special Issue Detection of Indoor Fungi: Part II)

11 pages, 1395 KiB

Open AccessEditor’s ChoiceReview

Prospects for Controlling Hepatitis B Globally

by Vicente Soriano, Víctor Moreno-Torres, Ana Treviño, Fernando de Jesús, Octavio Corral and Carmen de Mendoza

Pathogens 2024, 13(4), 291; https://doi.org/10.3390/pathogens13040291 - 29 Mar 2024

Cited by 2 | Viewed by 2824

Abstract

Infection with the hepatitis B virus (HBV) is highly prevalent globally. Over 250 million people suffer from chronic hepatitis B, and more than 800,000 patients die each year due to hepatitis B complications, including liver cancer. Although protective HBV vaccines are recommended for [...] Read more.

Infection with the hepatitis B virus (HBV) is highly prevalent globally. Over 250 million people suffer from chronic hepatitis B, and more than 800,000 patients die each year due to hepatitis B complications, including liver cancer. Although protective HBV vaccines are recommended for all newborns, global coverage is suboptimal. In adults, sexual transmission is by far the most frequent route of contagion. The WHO estimates that 1.5 million new HBV infections occur annually. Oral nucleos(t)ide analogues entecavir and tenofovir are the most frequent antivirals prescribed as HBV therapy. Almost all patients adherent to the medication achieve undetectable plasma viremia beyond 6 months of monotherapy. However, less than 5% achieve anti-HBs seroconversion, and viral rebound occurs following drug discontinuation. Therefore, nucleos(t)ide analogues need to be lifelong. New long-acting formulations of tenofovir and entecavir are being developed that will maximize treatment benefit and overcome adherence barriers. Furthermore, new antiviral agents are in development, including entry inhibitors, capside assembly modulators, and RNA interference molecules. The use of combination therapy pursues a functional HBV cure, meaning it is negative for both circulating HBV-DNA and HBsAg. Even when this goal is achieved, the cccDNA reservoir within infected hepatocytes remains a signal of past infection, and HBV can reactivate under immune suppression. Therefore, new gene therapies, including gene editing, are eagerly being pursued to silence or definitively disrupt HBV genomes within infected hepatocytes and, in this way, ultimately cure hepatitis B. At this time, three actions can be taken to push HBV eradication globally: (1) expand universal newborn HBV vaccination; (2) perform once-in-life testing of all adults to identify susceptible HBV persons that could be vaccinated (or re-vaccinated) and unveil asymptomatic carriers that could benefit from treatment; and (3) provide earlier antiviral therapy to chronic HBV carriers, as being aviremic reduces the risk of both clinical progression and transmission. Full article

(This article belongs to the Special Issue Viral Infections of Humans: Epidemiology and Control)

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23 pages, 3559 KiB

Open AccessEditor’s ChoiceArticle

Complete Rescue of HTLV-1_p12KO Infectivity by Depletion of Monocytes Together with NK and CD8⁺ T Cells

by Anna Gutowska, Sarkis Sarkis, Mohammad Arif Rahman, Katherine C. Goldfarbmuren, Ramona Moles, Massimiliano Bissa, Melvin Doster, Robyn Washington-Parks, Katherine McKinnon, Isabela Silva de Castro, Luca Schifanella, Genoveffa Franchini and Cynthia A. Pise-Masison

Pathogens 2024, 13(4), 292; https://doi.org/10.3390/pathogens13040292 - 29 Mar 2024

Viewed by 2398

Abstract

The transient depletion of monocytes alone prior to exposure of macaques to HTLV-1 enhances both HTLV-1_WT (wild type) and HTLV-1_p12KO (Orf-1 knockout) infectivity, but seroconversion to either virus is not sustained over time, suggesting a progressive decrease in virus expression. These [...] Read more.

The transient depletion of monocytes alone prior to exposure of macaques to HTLV-1 enhances both HTLV-1_WT (wild type) and HTLV-1_p12KO (Orf-1 knockout) infectivity, but seroconversion to either virus is not sustained over time, suggesting a progressive decrease in virus expression. These results raise the hypotheses that either HTLV-1 persistence depends on a monocyte reservoir or monocyte depletion provides a transient immune evasion benefit. To test these hypotheses, we simultaneously depleted NK cells, CD8⁺ T cells, and monocytes (triple depletion) prior to exposure to HTLV-1_WT or HTLV-1_p12KO. Remarkably, triple depletion resulted in exacerbation of infection by both viruses and complete rescue of HTLV-1_p12KO infectivity. Following triple depletion, we observed rapid and sustained seroconversion, high titers of antibodies against HTLV-1 p24Gag, and frequent detection of viral DNA in the blood and tissues of all animals when compared with depletion of only CD8⁺ and NK cells, or monocytes alone. The infection of macaques with HTLV-1_WT or HTLV-1_p12KO was associated with higher plasma levels of IL-10 after 21 weeks, while IL-6, IFN-γ, IL-18, and IL-1β were only elevated in animals infected with HTLV-1_WT. The repeat depletion of monocytes, NK, and CD8⁺ cells seven months following the first exposure to HTLV-1 did not further exacerbate viral replication. These results underscore the contribution of monocytes in orchestrating anti-viral immunity. Indeed, the absence of orf-1 expression was fully compensated by the simultaneous depletion of CD8⁺ T cells, NK cells, and monocytes, underlining the primary role of orf-1 in hijacking host immunity. Full article

(This article belongs to the Special Issue New Directions in HTLV-1 Research)

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16 pages, 1035 KiB

Open AccessEditor’s ChoiceReview

Zoonotic Threats: The (Re)emergence of Cercarial Dermatitis, Its Dynamics, and Impact in Europe

by Maria Teresa Bispo, Manuela Calado, Isabel Larguinho Maurício, Pedro Manuel Ferreira and Silvana Belo

Pathogens 2024, 13(4), 282; https://doi.org/10.3390/pathogens13040282 - 26 Mar 2024

Viewed by 2315

Abstract

Cercarial dermatitis (CD), or “Swimmer’s itch” as it is also known, is a waterborne illness caused by a blood fluke from the family Schistosomatidae. It occurs when cercariae of trematode species that do not have humans as their definitive host accidentally penetrate human [...] Read more.

Cercarial dermatitis (CD), or “Swimmer’s itch” as it is also known, is a waterborne illness caused by a blood fluke from the family Schistosomatidae. It occurs when cercariae of trematode species that do not have humans as their definitive host accidentally penetrate human skin (in an aquatic environment) and trigger allergic symptoms at the site of contact. It is an emerging zoonosis that occurs through water and is often overlooked during differential diagnosis. Some of the factors contributing to the emergence of diseases like CD are related to global warming, which brings about climate change, water eutrophication, the colonization of ponds by snails susceptible to the parasite, and sunlight exposure in the summer, associated with migratory bird routes. Therefore, with the increase in tourism, especially at fluvial beaches, it is relevant to analyze the current epidemiological scenario of CD in European countries and the potential regions at risk. Full article

(This article belongs to the Special Issue One Health and Neglected Zoonotic Diseases)

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11 pages, 466 KiB

Open AccessEditor’s ChoiceArticle

Revealing the Prevalence of Toxoplasma in Sierra Morena’s Wild Boar: An ELISA-Based Study Using Meat Juice

by José María Castillo-Castillo, Pablo José Rufino-Moya, Álvaro Martínez-Moreno, Ángela Salvador Castaño, Francisco Javier Martínez-Moreno and Rafael Zafra Leva

Pathogens 2024, 13(4), 281; https://doi.org/10.3390/pathogens13040281 - 26 Mar 2024

Viewed by 1267

Abstract

This research work focused on the prevalence of Toxoplasma gondii in wild boar from the Sierra Morena region. We conducted an ELISA analysis using meat juice samples. A total of 892 samples from six hunting seasons (2013–2019) were collected from the provinces that [...] Read more.

This research work focused on the prevalence of Toxoplasma gondii in wild boar from the Sierra Morena region. We conducted an ELISA analysis using meat juice samples. A total of 892 samples from six hunting seasons (2013–2019) were collected from the provinces that constitute the Sierra Morena Mountain range. These samples were analyzed using the Pigtype^® ELISA kit, specifically developed for detecting T. gondii in meat juice. The overall prevalence of T. gondii in Sierra Morena was 23.2%. The highest prevalences were observed in Córdoba (31.6%) and Jaén (25.9%). These provinces exhibit the highest density of wild boar as well as the greatest presence of the Iberian lynx (Lynx pardinus). Further in-depth studies are necessary, but it appears that the presence of wild felids and scavenger behavior may be associated with this observation. Full article

(This article belongs to the Special Issue Parasitic Diseases of Domestic, Wild, and Exotic Animals (Volume II))

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16 pages, 1302 KiB

Open AccessEditor’s ChoiceReview

Staphylococcus aureus Infections and Human Intestinal Microbiota

by Aotong Liu, Shari Garrett, Wanqing Hong and Jilei Zhang

Pathogens 2024, 13(4), 276; https://doi.org/10.3390/pathogens13040276 - 24 Mar 2024

Cited by 8 | Viewed by 5441

Abstract

Staphylococcus aureus (S. aureus) is a common pathogen that can cause many human diseases, such as skin infection, food poisoning, endocarditis, and sepsis. These diseases can be minor infections or life-threatening, requiring complex medical management resulting in substantial healthcare costs. Meanwhile, as [...] Read more.

Staphylococcus aureus (S. aureus) is a common pathogen that can cause many human diseases, such as skin infection, food poisoning, endocarditis, and sepsis. These diseases can be minor infections or life-threatening, requiring complex medical management resulting in substantial healthcare costs. Meanwhile, as the critically ignored “organ,” the intestinal microbiome greatly impacts physiological health, not only in gastrointestinal diseases but also in disorders beyond the gut. However, the correlation between S. aureus infection and intestinal microbial homeostasis is largely unknown. Here, we summarized the recent progress in understanding S. aureus infections and their interactions with the microbiome in the intestine. These summarizations will help us understand the mechanisms behind these infections and crosstalk and the challenges we are facing now, which could contribute to preventing S. aureus infections, effective treatment investigation, and vaccine development. Full article

(This article belongs to the Section Bacterial Pathogens)

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14 pages, 2824 KiB

Open AccessEditor’s ChoiceReview

Novel Oral Polio Vaccine Type 2 Use for Polio Outbreak Response: A Global Effort for a Global Health Emergency

by Feyrouz Damji Kurji, Ananda Sankar Bandyopadhyay, Simona Zipursky, Laura V. Cooper, Chris Gast, Margaret Toher, Ralf Clemens, Sue Ann Costa Clemens, Rayasam Prasad and Adriansjah Azhari

Pathogens 2024, 13(4), 273; https://doi.org/10.3390/pathogens13040273 - 23 Mar 2024

Cited by 2 | Viewed by 3712

Abstract

A sharp rise in circulating vaccine-derived poliovirus type 2 (cVDPV2) outbreaks in the years following the cessation of routine use of poliovirus type 2-containing oral polio vaccine and the trend of seeding new emergences with suboptimal vaccination response during the same time-period led [...] Read more.

A sharp rise in circulating vaccine-derived poliovirus type 2 (cVDPV2) outbreaks in the years following the cessation of routine use of poliovirus type 2-containing oral polio vaccine and the trend of seeding new emergences with suboptimal vaccination response during the same time-period led to the accelerated development of the novel oral polio vaccine type 2 (nOPV2), a vaccine with enhanced genetic stability and lower likelihood of reversion to neuroparalytic variants compared to its Sabin counterpart. In November 2020, nOPV2 became the first vaccine to be granted an Emergency Use Listing (EUL) by the World Health Organization (WHO) Prequalification Team (PQT), allowing close to a billion doses to be used by countries within three years after its first rollout and leading to full licensure and WHO prequalification (PQ) in December 2023. The nOPV2 development process exemplifies how scientific advances and innovative tools can be applied to combat global health emergencies in an urgent and adaptive way, building on a collaborative effort among scientific, regulatory and implementation partners and policymakers across the globe. Full article

(This article belongs to the Special Issue Human Poliovirus)

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14 pages, 1640 KiB

Open AccessEditor’s ChoiceArticle

Vector-Borne and Zoonotic Pathogens in Raccoon Dogs (Nyctereutes procyonoides) and Raccoons (Procyon lotor) from Schleswig-Holstein, Germany

by Jana C. Klink, Alexandra Rieger, Peter Wohlsein, Ursula Siebert and Anna Obiegala

Pathogens 2024, 13(3), 270; https://doi.org/10.3390/pathogens13030270 - 21 Mar 2024

Cited by 2 | Viewed by 1796

Abstract

Raccoon dogs (Nyctereutes procyonoides) and raccoons (Procyon lotor) are invasive alien species originating from East Asia and North America, respectively. They are discussed as vectors and reservoirs for various infectious diseases, including vector-borne and zoonotic pathogens, and are therefore [...] Read more.

Raccoon dogs (Nyctereutes procyonoides) and raccoons (Procyon lotor) are invasive alien species originating from East Asia and North America, respectively. They are discussed as vectors and reservoirs for various infectious diseases, including vector-borne and zoonotic pathogens, and are therefore a potential threat to human and domestic animal health, as well as to biodiversity and conservation. In the years 2021 and 2022, 110 raccoon dogs (Nyctereutes procyonoides) and 30 raccoons (Procyon lotor) were screened via qPCR for the presence of Leptospira spp., Rickettsia spp. and Borreliella spp. in the German federal state of Schleswig-Holstein as part of a health and risk assessment study. Borreliella spp. were confirmed in one raccoon dog and one raccoon, identified as Borreliella afzelii in the raccoon. Leptospira spp. were found in 21 (19.44%) raccoon dogs and 2 (6.90%) raccoons. In five raccoon dogs, Leptospira spp. were identified as Leptospira borgpetersenii, Leptospira kirschneri and Leptospira interrogans. Full article

(This article belongs to the Section Ticks)

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24 pages, 15946 KiB

Open AccessEditor’s ChoiceArticle

Characterization of a Novel Species of Legionella Isolated from a Healthcare Facility: Legionella resiliens sp. nov

by Sandra Cristino, Maria Rosaria Pascale, Federica Marino, Carlo Derelitto, Silvano Salaris, Massimiliano Orsini, Stefano Squarzoni, Antonella Grottola and Luna Girolamini

Pathogens 2024, 13(3), 250; https://doi.org/10.3390/pathogens13030250 - 14 Mar 2024

Cited by 1 | Viewed by 2287

Abstract

Two Legionella-like isolates, 8cVS16^T and 9fVS26, were isolated from a water distribution system (WDS) in a healthcare facility. Cells were Gram- and Ziehl Neelsen-stain-negative, rod-shaped, motile, and exhibited a blue-white fluorescence under Wood’s lamp at 365 nm. The strains grew in [...] Read more.

Two Legionella-like isolates, 8cVS16^T and 9fVS26, were isolated from a water distribution system (WDS) in a healthcare facility. Cells were Gram- and Ziehl Neelsen-stain-negative, rod-shaped, motile, and exhibited a blue-white fluorescence under Wood’s lamp at 365 nm. The strains grew in a range of 32–37 °C on BCYE with L-cysteine (Cys+), GVPC, and MWY agar medium, with a positive reaction for oxidase, catalase, and gelatinase. The dominant fatty acids were summed features 3 (C_16:1ω7c/C_16:1ω6c) (27.7%), C_16:0 iso (17.5%), and C_16:0 (16.3%), and Q13 as the major ubiquinone. The mip and rpoB gene sequences showed a similarity of 96.7% and 92.4%, with L. anisa (ATCC 35292^T). The whole genomes sequencing (WGS) performed displayed a GC content of 38.21 mol% for both. The digital DNA-DNA hybridization (dDDH) analysis demonstrated the separation of the two strains from the phylogenetically most related L. anisa (ATCC 35292^T), with ≤43% DNA-DNA relatedness. The Average Nucleotide Identity (ANI) between the two strains and L. anisa (ATCC 35292^T) was 90.74%, confirming that the two isolates represent a novel species of the genus Legionella. The name proposed for this species is Legionella resiliens sp. nov., with 8cVS16^T (=DSM 114356^T = CCUG 76627^T) as the type strain. Full article

(This article belongs to the Special Issue Bacterial Biofilm, Genomics and Virulence)

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16 pages, 6499 KiB

Open AccessEditor’s ChoiceArticle

Canine Schistosomiasis in the West Coast: Heterobilharzia americana in Two Natural Intermediate Hosts Found in the Colorado River, California

by Anil Baniya, Connor J. Goldy, Jiranun Ardpairin, Perla Achi, Yu Wei Chang, Rose C. Adrianza, Apichat Vitta and Adler R. Dillman

Pathogens 2024, 13(3), 245; https://doi.org/10.3390/pathogens13030245 - 13 Mar 2024

Viewed by 16179

Abstract

The emergence of infectious diseases presents a significant global health, economic, and security risk. Climate change can unexpectedly lead to the spread of pathogens, vectors, or hosts into new areas, contributing to the rise of infectious diseases. Surveillance plays a crucial role in [...] Read more.

The emergence of infectious diseases presents a significant global health, economic, and security risk. Climate change can unexpectedly lead to the spread of pathogens, vectors, or hosts into new areas, contributing to the rise of infectious diseases. Surveillance plays a crucial role in monitoring disease trends and implementing control strategies. In this study, we document the first discovery of Heterobilharzia americana, a parasitic schistosome of mammals and its intermediate hosts Galba cubensis and Galba humilis along the banks of the Colorado River in California. We conducted multiple samplings of snails from various locations in the region with a previous history of canine schistosomiasis. Nucleotide sequencing of the multiple regions of the snails’ and parasites’ DNA revealed the coexistence of G. cubensis and G. humilis, both infected with H. americana. Phylogenetic analyses further validate the presence of H. americana in California, suggesting a wider distribution than previously reported. Our findings have implications for public health, veterinary medicine, and biodiversity conservation, contributing to developing effective control strategies to prevent the spread of this emerging infectious disease. Full article

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

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22 pages, 2173 KiB

Open AccessEditor’s ChoiceReview

Viral Infections, Are They a Trigger and Risk Factor of Alzheimer’s Disease?

by Meagan D. Rippee-Brooks, Wenzhe Wu, Jianli Dong, Miguel Pappolla, Xiang Fang and Xiaoyong Bao

Pathogens 2024, 13(3), 240; https://doi.org/10.3390/pathogens13030240 - 8 Mar 2024

Cited by 3 | Viewed by 3138

Abstract

Alzheimer’s Disease (AD), a progressive and debilitating condition, is reported to be the most common type of dementia, with at least 55 million people believed to be currently affected. Many causation hypotheses of AD exist, yet the intriguing link between viral infection and [...] Read more.

Alzheimer’s Disease (AD), a progressive and debilitating condition, is reported to be the most common type of dementia, with at least 55 million people believed to be currently affected. Many causation hypotheses of AD exist, yet the intriguing link between viral infection and its possible contribution to the known etiology of AD has become an attractive focal point of research for the field and a challenging study task. In this review, we will explore the historical perspective and milestones that led the field to investigate the viral connection to AD. Specifically, several viruses such as Herpes Simplex Virus 1 (HSV-1), Zika virus (ZIKV), and severe cute respiratory syndrome coronavirus 2 (SARS-CoV-2), along with several others mentioned, include the various viruses presently considered within the field. We delve into the strong evidence implicating these viruses in the development of AD such as the lytic replication and axonal transport of HSV-1, the various mechanisms of ZIKV neurotropism through the human protein Musashi-1 (MSI1), and the spread of SARS-CoV-2 through the transfer of the virus through the BBB endothelial cells to glial cells and then to neurons via transsynaptic transfer. We will also explore beyond these mere associations by carefully analyzing the potential mechanisms by which these viruses may contribute to AD pathology. This includes but is not limited to direct neuronal infections, the dysregulation of immune responses, and the impact on protein processing (Aβ42 and hyperphosphorylated tau). Controversies and challenges of the virus–AD relationship emerge as we tease out these potential mechanisms. Looking forward, we emphasize future directions, such as distinct questions and proposed experimentations to explore, that the field should take to tackle the remaining unanswered questions and the glaring research gaps that persist. Overall, this review aims to provide a comprehensive survey of the past, present, and future of the potential link between viral infections and their association with AD development while encouraging further discussion. Full article

(This article belongs to the Special Issue Viral Infections and Their Effects on the Central Nervous System (CNS))

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12 pages, 321 KiB

Open AccessEditor’s ChoiceArticle

Hunting for Answers: Assessing Brucella spp. Seroprevalence and Risks in Red Deer and Wild Boar in Central Portugal

by Humberto Pires, Luís Cardoso, Ana Patrícia Lopes, Maria da Conceição Fontes, Sérgio Santos-Silva, Manuela Matos, Cristina Pintado, Natália Roque, Leonardo Filipe Fonseca, Inês Morgado, Ana Sofia Dias, Luís Figueira, Ana Cristina Matos, João Rodrigo Mesquita and Ana Cláudia Coelho

Pathogens 2024, 13(3), 242; https://doi.org/10.3390/pathogens13030242 - 8 Mar 2024

Cited by 2 | Viewed by 1904

Abstract

Between 2016 and 2023, a cross-sectional study was conducted in the central region of Portugal in order to better understand the epidemiology and public health risks resulting from the handling and consumption of game animals infected with Brucella spp. The seroprevalence and risk [...] Read more.

Between 2016 and 2023, a cross-sectional study was conducted in the central region of Portugal in order to better understand the epidemiology and public health risks resulting from the handling and consumption of game animals infected with Brucella spp. The seroprevalence and risk factors for Brucella spp. seropositivity were evaluated. Antibodies against Brucella spp. were determined using a commercial enzyme-linked immunosorbent assay (ELISA) according to the manufacturer’s instructions. Results showed that in the 650 serum samples collected from red deer (n = 298) and wild boars (n = 352) in Portugal, 21.7% (n = 141; 95% CI: 18.6–25.1%) tested positive. Wild boar had a significantly higher prevalence (35.5%; 95% CI: 30.5–40.8%) than red deer (5.4%, 95% CI: 3.1–8.6%; p ≤ 0.001). Risk factors for seropositivity were investigated using multivariable logistic regression models. The odds of being seropositive was 8.39 (95% CI: 4.75–14.84; p ≤ 0.001) times higher in wild boar than in red deer. Correlations between sex, age, body condition, and seropositivity could not be observed. The higher seroprevalence in wild boar suggests that this species may primarily contribute to the Brucella spp. ecology in central Portugal. Full article

(This article belongs to the Special Issue Epidemiology and Outcomes Research in Infectious Diseases)

22 pages, 4163 KiB

Open AccessEditor’s ChoiceReview

Current Knowledge of Enterococcal Endocarditis: A Disease Lurking in Plain Sight of Health Providers

by Francesco Nappi

Pathogens 2024, 13(3), 235; https://doi.org/10.3390/pathogens13030235 - 7 Mar 2024

Cited by 4 | Viewed by 2621

Abstract

Enterococcus faecalis is a bacterial pathogen that can cause opportunistic infections. Studies indicate that initial biofilm formation plays a crucial regulatory role in these infections, as well as in colonising and maintaining the gastrointestinal tract as a commensal member of the microbiome of [...] Read more.

Enterococcus faecalis is a bacterial pathogen that can cause opportunistic infections. Studies indicate that initial biofilm formation plays a crucial regulatory role in these infections, as well as in colonising and maintaining the gastrointestinal tract as a commensal member of the microbiome of most land animals. It has long been thought that vegetation of endocarditis resulting from bacterial attachment to the endocardial endothelium requires some pre-existing tissue damage, and in animal models of experimental endocarditis, mechanical valve damage is typically induced by cardiac catheterisation preceding infection. This section reviews historical and contemporary animal model studies that demonstrate the ability of E. faecalis to colonise the undamaged endovascular endothelial surface directly and produce robust microcolony biofilms encapsulated within a bacterially derived extracellular matrix. This report reviews both previous and current animal model studies demonstrating the resilient capacity of E. faecalis to colonise the undamaged endovascular endothelial surface directly and produce robust microcolony biofilms encapsulated in a bacterially derived extracellular matrix. The article also considers the morphological similarities when these biofilms develop on different host sites, such as when E. faecalis colonises the gastrointestinal epithelium as a commensal member of the common vertebrate microbiome, lurking in plain sight and transmitting systemic infection. These phenotypes may enable the organism to survive as an unrecognised infection in asymptomatic subjects, providing an infectious resource for subsequent clinical process of endocarditis. Full article

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11 pages, 1606 KiB

Open AccessEditor’s ChoiceArticle

Inflammatory CD11b⁺ Macrophages Produce BAFF in Spleen of Mice Infected with Leishmania donovani

by Kazuki Nagai, Wataru Fujii, Junya Yamagishi, Chizu Sanjoba and Yasuyuki Goto

Pathogens 2024, 13(3), 232; https://doi.org/10.3390/pathogens13030232 - 6 Mar 2024

Cited by 1 | Viewed by 2358

Abstract

Visceral leishmaniasis (VL) is an infectious disease caused by parasitic protozoa of the genus Leishmania and manifests clinical symptoms such as splenomegaly, hepatomegaly, anemia, and fever. It has previously been shown that B-cell-activating factor (BAFF) is involved in splenomegaly during VL. Although BAFF [...] Read more.

Visceral leishmaniasis (VL) is an infectious disease caused by parasitic protozoa of the genus Leishmania and manifests clinical symptoms such as splenomegaly, hepatomegaly, anemia, and fever. It has previously been shown that B-cell-activating factor (BAFF) is involved in splenomegaly during VL. Although BAFF is known to be expressed by a variety of cells, the mechanism of elevated BAFF expression in VL is not clear. In this study, we aimed to identify BAFF-producing cells in the spleens of mice infected with Leishmania donovani. Splenocytes of L. donovani-infected mice showed elevated BAFF expression compared to that of naive mice. In the infected spleen, the number of both CD11b⁺ and F4/80⁺ cells increased, and the major BAFF-producing cells were CD11b⁺ cells, which did not serve as host cells of Leishmania. Immunohistochemical/immunofluorescent staining of spleens of infected mice revealed that the increased CD11b⁺ cells were primarily MRP14⁺ mononuclear cells. Together, these results suggest the increased BAFF expression in the spleen of L. donovani-infected mice involves a recruitment of inflammatory macrophages distinct from host macrophages for the parasites. Full article

(This article belongs to the Special Issue Leishmaniasis: Transmission, Pathogenesis and Treatment)

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13 pages, 1633 KiB

Open AccessEditor’s ChoiceArticle

Genetic Diversification and Resistome of Coagulase-Negative Staphylococci from Nostrils of Healthy Dogs and Dog-Owners in La Rioja, Spain

by Idris Nasir Abdullahi, Carmen Lozano, Carmen González-Azcona, Myriam Zarazaga and Carmen Torres

Pathogens 2024, 13(3), 229; https://doi.org/10.3390/pathogens13030229 - 5 Mar 2024

Cited by 2 | Viewed by 1678

Abstract

Coagulase-negative staphylococci (CoNS) species in healthy dogs and their owners could be transferred between these hosts and carry diverse antimicrobial resistance (AMR) genes of public health concern. This study determined the frequency, diversity, and AMR genes of nasal CoNS from healthy dogs and [...] Read more.

Coagulase-negative staphylococci (CoNS) species in healthy dogs and their owners could be transferred between these hosts and carry diverse antimicrobial resistance (AMR) genes of public health concern. This study determined the frequency, diversity, and AMR genes of nasal CoNS from healthy dogs and in-contact people as well as the rate of intra-household (between healthy dogs and dog-owners) transmission of CoNS. Nasal samples were collected and processed from 34 dogs and 41 humans from 27 households, and CoNS identification was done by MALDI-TOF-MS. The AMR determinants and genetic lineages were determined by PCR/sequencing. A total of 216 CoNS isolates were initially obtained and identified, and the AMR phenotypes were determined. From these, 130 non-repetitive CoNS were selected (one isolate of each species per sample or more than one if they presented different AMR phenotypes) and further characterized. The predominant species from dog carriers were S. epidermidis (26.5%), S. hominis (8.8%), and S. cohnii (8.8%), whereas in the human carriers, the predominant ones were S. epidermidis (80.4%), S. lugdunensis (9.8%), and S. hominis (9.8%). Intra-host species diversity (>one CoNS species) was detected in 37.5% of dogs and 21.6% of dog-owners. Conversely, 50% of dogs and 70.3% of dog-owners had intra-species AMR diversity (2–4 AMR-CoNS profiles). About 20% were susceptible to all antimicrobial agents tested, 31.5% displayed a multidrug resistance phenotype, and 17.4% were mecA-positive, located in SCCmec type V (24.2%), III (18.1%), IVc (12.1%), and II (6.1%). The other mec-A positive CoNS isolates (39.5%) had non-typeable SCCmec. The highest AMR rates were found against erythromycin (32.3%/mph(C), msr(A)) and mupirocin (20.8%/mupA), but the resistance rates for other antimicrobial agents were <10% each. Remarkably, one linezolid-resistant S. epidermidis-ST35 isolate was identified and mediated by four amino acid substitutions in L3 and one in L4 ribosomal proteins. Dogs and dog-owners as carriers of S. epidermidis with similar AMR patterns and genetic lineages (ST59, ST61, ST166 and ST278) were detected in four households (14.8%). Diverse CoNS carriage and moderate level of AMR were obtained from this study. The detection of CoNS carrying diverse SCCmec elements and intra-species AMR diversity highlights the roles of dog ownership in the potential transmission of antimicrobial-resistant CoNS in either direction. Full article

(This article belongs to the Section Bacterial Pathogens)

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12 pages, 2698 KiB

Open AccessEditor’s ChoiceArticle

Porcine Monocyte DNA Traps Formed during Infection with Pathogenic Clostridioides difficile Strains

by Jade Lawrence, Paul Barrow and Neil Foster

Pathogens 2024, 13(3), 228; https://doi.org/10.3390/pathogens13030228 - 5 Mar 2024

Viewed by 1643

Abstract

Clostridioides (Clostridium) difficile is an enteric pathogen of several mammalian species including man, frequently involving nosocomial resurgence, following oral administration of broad-spectrum antibiotics, but also with human-to-human infection occurring, and neonatal pigs with zoonotic transmission. To date, the immune response to [...] Read more.

Clostridioides (Clostridium) difficile is an enteric pathogen of several mammalian species including man, frequently involving nosocomial resurgence, following oral administration of broad-spectrum antibiotics, but also with human-to-human infection occurring, and neonatal pigs with zoonotic transmission. To date, the immune response to C. difficile has mostly focused on neutrophils and cytokine/chemokines, particularly in human infection. The neonatal pig is now recognized as a valuable model for human infection. We show that porcine monocytes respond to C. difficile differently compared with many other bacterial infections. Infection of porcine monocytes with human C. difficile strains CD630 (Ribotype 078) or R20291 (Ribotype 027) for 3 or 24 h post-infection (pi) resulted in a lack of oxidative burst or nitrite ion production when compared to uninfected controls (p > 0.05). The survival dynamics of both CD630 and R20291 in monocytes were similar with intracellular bacterial numbers being similar at 3 h pi and 24 h pi (p > 0.05). However, we show that porcine monocytes entrap C. difficile via extracellular DNA traps. This process began as early as 3 h pi, and at 24 h pi the nuclei appeared to be depleted of DNA, although extracellular DNA was associated with the cell membrane. Our preliminary study also suggests that entrapment of C. difficile by extracellular DNA may occur via a process of monocyte etosis. Full article

(This article belongs to the Section Immunological Responses and Immune Defense Mechanisms)

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10 pages, 490 KiB

Open AccessEditor’s ChoiceArticle

Infant Non-Secretor Histoblood Group Antigen Phenotype Reduces Susceptibility to Both Symptomatic and Asymptomatic Rotavirus Infection

by Benjamin Lee, Md Abdul Kader, Masud Alam, Dorothy M. Dickson, Patrick Harvey, E. Ross Colgate, Mami Taniuchi, William A. Petri, Jr., Rashidul Haque and Beth D. Kirkpatrick

Pathogens 2024, 13(3), 223; https://doi.org/10.3390/pathogens13030223 - 4 Mar 2024

Viewed by 1930

Abstract

The infant non-secretor histoblood group antigen phenotype is associated with reduced risk of symptomatic rotavirus diarrhea, one of the leading global causes of severe pediatric diarrheal disease and mortality. However, little is known regarding the role of secretor status in asymptomatic rotavirus infections. [...] Read more.

The infant non-secretor histoblood group antigen phenotype is associated with reduced risk of symptomatic rotavirus diarrhea, one of the leading global causes of severe pediatric diarrheal disease and mortality. However, little is known regarding the role of secretor status in asymptomatic rotavirus infections. Therefore, we performed a nested case–control study within a birth cohort study previously conducted in Dhaka, Bangladesh, to determine the association between infant secretor phenotype and the odds of asymptomatic rotavirus infection, in addition to the risk of rotavirus diarrhea, in unvaccinated infants. In the parent cohort, infants were enrolled in the first week of life and followed through the first two years of life with multiple clinic visits and active surveillance for diarrheal illness. Secretor phenotyping was performed on saliva. Eleven surveillance stools collected over the first year of life were tested for rotavirus by real-time RT-PCR, followed by conventional PCR and amplicon sequencing to identify the infecting P-type of positive specimens. Similar to findings for symptomatic diarrhea, infant non-secretors experienced significantly fewer primary episodes of asymptomatic rotavirus infection through the first year of life in a likely rotavirus P-genotype-dependent manner. These data suggest that non-secretors experienced reduced risk from rotavirus due to decreased susceptibility to infection rather than reduced infection severity. Full article

(This article belongs to the Special Issue Burden, Prevention, and Control of Enteric Viral Infections)

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16 pages, 1667 KiB

Open AccessEditor’s ChoiceReview

Inactivated Poliovirus Vaccine: Recent Developments and the Tortuous Path to Global Acceptance

by Roland W. Sutter, Martin Eisenhawer, Natalia A. Molodecky, Harish Verma and Hiromasa Okayasu

Pathogens 2024, 13(3), 224; https://doi.org/10.3390/pathogens13030224 - 4 Mar 2024

Cited by 2 | Viewed by 2869

Abstract

Inactivated poliovirus vaccine (IPV), available since 1955, became the first vaccine to be used to protect against poliomyelitis. While the immunogenicity of IPV to prevent paralytic poliomyelitis continues to be irrefutable, its requirement for strong containment (due to large quantities of live virus [...] Read more.

Inactivated poliovirus vaccine (IPV), available since 1955, became the first vaccine to be used to protect against poliomyelitis. While the immunogenicity of IPV to prevent paralytic poliomyelitis continues to be irrefutable, its requirement for strong containment (due to large quantities of live virus used in the manufacturing process), perceived lack of ability to induce intestinal mucosal immunity, high cost and increased complexity to administer compared to oral polio vaccine (OPV), have limited its use in the global efforts to eradicate poliomyelitis. In order to harvest the full potential of IPV, a program of work has been carried out by the Global Polio Eradication Initiative (GPEI) over the past two decades that has focused on: (1) increasing the scientific knowledge base of IPV; (2) translating new insights and evidence into programmatic action; (3) expanding the IPV manufacturing infrastructure for global demand; and (4) continuing to pursue an ambitious research program to develop more immunogenic and safer-to-produce vaccines. While the knowledge base of IPV continues to expand, further research and product development are necessary to ensure that the program priorities are met (e.g., non-infectious production through virus-like particles, non-transmissible vaccine inducing humoral and intestinal mucosal immunity and new methods for house-to-house administration through micro-needle patches and jet injectors), the discussions have largely moved from whether to how to use this vaccine most effectively. In this review, we summarize recent developments on expanding the science base of IPV and provide insight into policy development and the expansion of IPV manufacturing and production, and finally we provide an update on the current priorities. Full article

(This article belongs to the Special Issue Human Poliovirus)

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10 pages, 354 KiB

Open AccessEditor’s ChoiceArticle

Hepatitis C Epidemiology: Insights from a Comprehensive Cohort Study in ASST Melegnano and Martesana, Lombardia Region, Northern Italy

by Michele Nardone, Dario Di Stasio, Alberta Lucchese, Daniele Gentili, Giulia Cattabianchi, Carlo Signorelli, Pierangelo Sarchi, Giovanna Pulcrano, Valentino Lembo, Paola Maria Pirola, Dorina Lauritano and Francesco Carinci

Pathogens 2024, 13(3), 215; https://doi.org/10.3390/pathogens13030215 - 28 Feb 2024

Viewed by 1440

Abstract

Hepatitis C virus (HCV) infection is a significant public health problem affecting 58 million people worldwide, including 3.9 million in Europe. Many of these infections go undiagnosed because chronic infection is often asymptomatic. This observational cohort study presents a detailed examination of hepatitis [...] Read more.

Hepatitis C virus (HCV) infection is a significant public health problem affecting 58 million people worldwide, including 3.9 million in Europe. Many of these infections go undiagnosed because chronic infection is often asymptomatic. This observational cohort study presents a detailed examination of hepatitis C virus epidemiology in Lombardia (Italy) and was conducted within the ASST “Melegnano e della Martesana”. The study involved comprehensive HCV screening of 3290 patients accessing the collection points and/or hospitalized in the facilities of the ASST from 20 May 2022 to 13 April 2023. Screening was conducted using serological assays. The prevalence of anti-HCV-positive patients (HCV-Ab) and then HCV-positive patients (RNA) was calculated. Chi-square tests examined the associations between continuous and categorical variables. Logistic regression was used to evaluate the influence of demographic and geographic variables as predictors of HCV positivity. The study revealed an overall HCV-Ab prevalence of 0.912% (CI (0.59–1.24%)) in the examined cohort, of whom 15.15% (two females and three males) were positive for HCV RNA. The prevalence of HCV RNA positivity was 0.152% (CI (0.05–0.35%)). Sex disparity was evident, with male patients exhibiting a higher prevalence compared to females, confirmed by logistic regression (0.0147 vs. 0.0061–OR = 2.44; CI (0.0059–0.0124)). Age stratification indicated an ascending trend in prevalence with age, peaking at 1.35% in individuals aged over 50. These findings underscore the critical need for targeted HCV screening, contributing valuable insights to the global epidemiology of HCV in the era of DAAs. Full article

(This article belongs to the Section Epidemiology of Infectious Diseases)

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