Editor’s Choice Articles

Editor’s Choice articles are based on recommendations by the scientific editors of MDPI journals from around the world. Editors select a small number of articles recently published in the journal that they believe will be particularly interesting to readers, or important in the respective research area. The aim is to provide a snapshot of some of the most exciting work published in the various research areas of the journal.

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19 pages, 1079 KiB  
Review
Using Serological Markers for the Surveillance of Plasmodium vivax Malaria: A Scoping Review
by Lejla Kartal, Ivo Mueller and Rhea J. Longley
Pathogens 2023, 12(6), 791; https://doi.org/10.3390/pathogens12060791 - 31 May 2023
Cited by 5 | Viewed by 4494
Abstract
The utilisation of serological surveillance methods for malaria has the potential to identify individuals exposed to Plasmodium vivax, including asymptomatic carriers. However, the application of serosurveillance varies globally, including variations in methodology and transmission context. No systematic review exists describing the advantages [...] Read more.
The utilisation of serological surveillance methods for malaria has the potential to identify individuals exposed to Plasmodium vivax, including asymptomatic carriers. However, the application of serosurveillance varies globally, including variations in methodology and transmission context. No systematic review exists describing the advantages and disadvantages of utilising serosurveillance in various settings. Collation and comparison of these results is a necessary first step to standardise and validate the use of serology for the surveillance of P. vivax in specific transmission contexts. A scoping review was performed of P. vivax serosurveillance applications globally. Ninety-four studies were found that met predefined inclusion and exclusion criteria. These studies were examined to determine the advantages and disadvantages of serosurveillance experienced in each study. If studies reported seroprevalence results, this information was also captured. Measurement of antibodies serves as a proxy by which individuals exposed to P. vivax may be indirectly identified, including those with asymptomatic infections, which may be missed by other technologies. Other thematic advantages identified included the ease and simplicity of serological assays compared to both microscopy and molecular diagnostics. Seroprevalence rates varied widely from 0–93%. Methodologies must be validated across various transmission contexts to ensure the applicability and comparability of results. Other thematic disadvantages identified included challenges with species cross-reactivity and determining changes in transmission patterns in both the short- and long-term. Serosurveillance requires further refinement to be fully realised as an actionable tool. Some work has begun in this area, but more is required. Full article
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12 pages, 1372 KiB  
Article
Fluconazole Resistance and Virulence in In Vitro Induced-Fluconazole Resistant Strains and in Clinical Fluconazole Resistant Strain of Cryptococcus deuterogattii
by Sébastien Bertout, Laetitia Laroche, Frédéric Roger, Donika Krasteva, Pascal Drakulovski and Virginie Bellet
Pathogens 2023, 12(6), 758; https://doi.org/10.3390/pathogens12060758 - 24 May 2023
Cited by 2 | Viewed by 2501
Abstract
Neuromeningeal cryptococcosis is a life-threatening infection of the central nervous system, caused by encapsulated yeast belonging to the Cryptococcus neoformans and Cryptococcus gattii species complexes. Recent data showed that virulence and antifungal resistance are variable for yeasts belonging to the C. gattii species [...] Read more.
Neuromeningeal cryptococcosis is a life-threatening infection of the central nervous system, caused by encapsulated yeast belonging to the Cryptococcus neoformans and Cryptococcus gattii species complexes. Recent data showed that virulence and antifungal resistance are variable for yeasts belonging to the C. gattii species complex. There is an increase in resistance to fluconazole for yeasts of the C. gattii species complex and the virulence is variable according to the genotype. In the present study, (i) we explored and compared the mechanisms of resistance to fluconazole between C. deuterogattii clinically resistant strains and induced fluconazole-resistant strains by exposure to fluconazole in vitro, and (ii) we studied their virulence in the Galleria mellonella study model. We demonstrated that the fluconazole resistance mechanisms involved were different between clinically resistant strains and induced resistant strains. We also demonstrated that fluconazole-induced resistant strains are less virulent when compared to the original susceptible strains. On the contrary, the clinically resistant strain tested maintains its virulence compared to fluconazole-susceptible strains of the same sequence type. Full article
(This article belongs to the Special Issue Advanced Research on Cryptococcus and Cryptococcosis)
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18 pages, 3142 KiB  
Article
Mapping the Dynamics of Contemporary PRRSV-2 Evolution and Its Emergence and Spreading Hotspots in the U.S. Using Phylogeography
by Nakarin Pamornchainavakul, Igor A. D. Paploski, Dennis N. Makau, Mariana Kikuti, Albert Rovira, Samantha Lycett, Cesar A. Corzo and Kimberly VanderWaal
Pathogens 2023, 12(5), 740; https://doi.org/10.3390/pathogens12050740 - 20 May 2023
Cited by 6 | Viewed by 3892
Abstract
The repeated emergence of new genetic variants of PRRSV-2, the virus that causes porcine reproductive and respiratory syndrome (PRRS), reflects its rapid evolution and the failure of previous control efforts. Understanding spatiotemporal heterogeneity in variant emergence and spread is critical for future outbreak [...] Read more.
The repeated emergence of new genetic variants of PRRSV-2, the virus that causes porcine reproductive and respiratory syndrome (PRRS), reflects its rapid evolution and the failure of previous control efforts. Understanding spatiotemporal heterogeneity in variant emergence and spread is critical for future outbreak prevention. Here, we investigate how the pace of evolution varies across time and space, identify the origins of sub-lineage emergence, and map the patterns of the inter-regional spread of PRRSV-2 Lineage 1 (L1)—the current dominant lineage in the U.S. We performed comparative phylogeographic analyses on subsets of 19,395 viral ORF5 sequences collected across the U.S. and Canada between 1991 and 2021. The discrete trait analysis of multiple spatiotemporally stratified sampled sets (n = 500 each) was used to infer the ancestral geographic region and dispersion of each sub-lineage. The robustness of the results was compared to that of other modeling methods and subsampling strategies. Generally, the spatial spread and population dynamics varied across sub-lineages, time, and space. The Upper Midwest was a main spreading hotspot for multiple sub-lineages, e.g., L1C and L1F, though one of the most recent emergence events (L1A(2)) spread outwards from the east. An understanding of historical patterns of emergence and spread can be used to strategize disease control and the containment of emerging variants. Full article
(This article belongs to the Special Issue Spatio-Temporal Analysis of Veterinary Infectious Diseases)
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18 pages, 1641 KiB  
Systematic Review
Systematic Review and Meta-Analysis of the Efficacy and Effectiveness of Pneumococcal Vaccines in Adults
by Jennifer L. Farrar, Lana Childs, Mahamoudou Ouattara, Fahmina Akhter, Amadea Britton, Tamara Pilishvili and Miwako Kobayashi
Pathogens 2023, 12(5), 732; https://doi.org/10.3390/pathogens12050732 - 19 May 2023
Cited by 17 | Viewed by 4236
Abstract
New pneumococcal conjugate vaccines (PCVs), 15- and 20-valent (PCV15 and PCV20), have been licensed for use among U.S. adults based on safety and immunogenicity data compared with the previously recommended 13-valent PCV (PCV13) and 23-valent pneumococcal polysaccharide vaccines (PPSV23). We conducted a systematic [...] Read more.
New pneumococcal conjugate vaccines (PCVs), 15- and 20-valent (PCV15 and PCV20), have been licensed for use among U.S. adults based on safety and immunogenicity data compared with the previously recommended 13-valent PCV (PCV13) and 23-valent pneumococcal polysaccharide vaccines (PPSV23). We conducted a systematic review of the literature on PCV13 and PPSV23 efficacy (randomized controlled trials [RCTs]) or effectiveness (observational studies) against vaccine type (PCV13 type or PPSV23 type, respectively), invasive pneumococcal disease (IPD), and pneumococcal pneumonia (PP) in adults. We utilized the search strategy from a previous systematic review of the literature published during the period from January 2016 to April 2019, and updated the search through March 2022. The certainty of evidence was assessed using the Cochrane risk-of-bias 2.0 tool and the Newcastle–Ottawa scale. When feasible, meta-analyses were conducted. Of the 5085 titles identified, 19 studies were included. One RCT reported PCV13 efficacy of 75% (PCV13-type IPD) and 45% (PCV13-type PP). Three studies each reported PCV13 effectiveness against PCV13-type IPD (range 47% to 68%) and against PCV13-type PP (range 38% to 68%). The pooled PPSV23 effectiveness was 45% (95% CI: 37%, 51%) against PPSV23-type IPD (nine studies) and 18% (95% CI: −4%, 35%) against PPSV23-type PP (five studies). Despite the heterogeneity across studies, our findings suggest that PCV13 and PPSV23 protect against VT-IPD and VT-PP in adults. Full article
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22 pages, 2064 KiB  
Review
Mechanisms of Innate Immune Sensing of HTLV-1 and Viral Immune Evasion
by Suchitra Mohanty and Edward W. Harhaj
Pathogens 2023, 12(5), 735; https://doi.org/10.3390/pathogens12050735 - 19 May 2023
Cited by 3 | Viewed by 4395
Abstract
Human T lymphotropic virus-1 (HTLV-1) was the first identified oncoretrovirus, which infects and establishes a persistent infection in approximately 10–20 million people worldwide. Although only ~5% of infected individuals develop pathologies such as adult T-cell leukemia/lymphoma (ATLL) or a neuroinflammatory disorder termed HTLV-1-asssociated [...] Read more.
Human T lymphotropic virus-1 (HTLV-1) was the first identified oncoretrovirus, which infects and establishes a persistent infection in approximately 10–20 million people worldwide. Although only ~5% of infected individuals develop pathologies such as adult T-cell leukemia/lymphoma (ATLL) or a neuroinflammatory disorder termed HTLV-1-asssociated myelopathy/tropical spastic paraparesis (HAM/TSP), asymptomatic carriers are more susceptible to opportunistic infections. Furthermore, ATLL patients are severely immunosuppressed and prone to other malignancies and other infections. The HTLV-1 replication cycle provides ligands, mainly nucleic acids (RNA, RNA/DNA intermediates, ssDNA intermediates, and dsDNA), that are sensed by different pattern recognition receptors (PRRs) to trigger immune responses. However, the mechanisms of innate immune detection and immune responses to HTLV-1 infection are not well understood. In this review, we highlight the functional roles of different immune sensors in recognizing HTLV-1 infection in multiple cell types and the antiviral roles of host restriction factors in limiting persistent infection of HTLV-1. We also provide a comprehensive overview of intricate strategies employed by HTLV-1 to subvert the host innate immune response that may contribute to the development of HTLV-1-associated diseases. A more detailed understanding of HTLV-1-host pathogen interactions may inform novel strategies for HTLV-1 antivirals, vaccines, and treatments for ATLL or HAM/TSP. Full article
(This article belongs to the Special Issue Human T-cell Leukemia Virus Type 1 (HTLV-1))
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10 pages, 5234 KiB  
Communication
Morphologic and Genetic Analysis of Synhimantus (Synhimantus) laticeps from a Long-Eared Owl (Asio otus)
by Carolina Lopes, Sérgio Santos-Silva, Carolina Nunes, Susana Mendes, Catarina Costa, Erica Brazio, Teresa Coutinho, Filipa Teixeira Rodrigues, João R. Mesquita, Ana Cláudia Coelho, Luís Cardoso and Ana Patrícia Lopes
Pathogens 2023, 12(5), 717; https://doi.org/10.3390/pathogens12050717 - 15 May 2023
Viewed by 1903
Abstract
The long-eared owl (Asio otus) is a medium-sized owl species that is well-distributed in almost all of the territories in Portugal. Nematodes were found in the oral cavity of a long-eared owl (A. otus) admitted to CRASSA (Wildlife Rehabilitation [...] Read more.
The long-eared owl (Asio otus) is a medium-sized owl species that is well-distributed in almost all of the territories in Portugal. Nematodes were found in the oral cavity of a long-eared owl (A. otus) admitted to CRASSA (Wildlife Rehabilitation Centre of Santo André). During a physical exam and stabilization of the bird, five nematodes were collected. The worms were examined and measured under light microscopy, and photos were taken. After a morphological analysis was conducted, all the nematodes (five females) were identified as Synhimantus (Synhimantus) laticeps. Two specimens were subjected to molecular analysis, which confirmed the result. This study provides a combined morphological and genetic approach to S. laticeps. To the authors’ best knowledge, this is the first report including genetic sequencing of S. laticeps in a long-eared owl (A. otus) from Portugal. Full article
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36 pages, 3850 KiB  
Review
Mice as an Animal Model for Japanese Encephalitis Virus Research: Mouse Susceptibility, Infection Route, and Viral Pathogenesis
by Jordan C. Frank, Byung-Hak Song and Young-Min Lee
Pathogens 2023, 12(5), 715; https://doi.org/10.3390/pathogens12050715 - 14 May 2023
Cited by 3 | Viewed by 3192
Abstract
Japanese encephalitis virus (JEV), a zoonotic flavivirus, is principally transmitted by hematophagous mosquitoes, continually between susceptible animals and incidentally from those animals to humans. For almost a century since its discovery, JEV was geographically confined to the Asia-Pacific region with recurrent sizable outbreaks [...] Read more.
Japanese encephalitis virus (JEV), a zoonotic flavivirus, is principally transmitted by hematophagous mosquitoes, continually between susceptible animals and incidentally from those animals to humans. For almost a century since its discovery, JEV was geographically confined to the Asia-Pacific region with recurrent sizable outbreaks involving wildlife, livestock, and people. However, over the past decade, it has been detected for the first time in Europe (Italy) and Africa (Angola) but has yet to cause any recognizable outbreaks in humans. JEV infection leads to a broad spectrum of clinical outcomes, ranging from asymptomatic conditions to self-limiting febrile illnesses to life-threatening neurological complications, particularly Japanese encephalitis (JE). No clinically proven antiviral drugs are available to treat the development and progression of JE. There are, however, several live and killed vaccines that have been commercialized to prevent the infection and transmission of JEV, yet this virus remains the main cause of acute encephalitis syndrome with high morbidity and mortality among children in the endemic regions. Therefore, significant research efforts have been directed toward understanding the neuropathogenesis of JE to facilitate the development of effective treatments for the disease. Thus far, multiple laboratory animal models have been established for the study of JEV infection. In this review, we focus on mice, the most extensively used animal model for JEV research, and summarize the major findings on mouse susceptibility, infection route, and viral pathogenesis reported in the past and present, and discuss some unanswered key questions for future studies. Full article
(This article belongs to the Special Issue Comparative Animal Models of Human Viral Infections)
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10 pages, 606 KiB  
Perspective
Does Experimental Reduction of Blacklegged Tick (Ixodes scapularis) Abundance Reduce Lyme Disease Incidence?
by Richard S. Ostfeld and Felicia Keesing
Pathogens 2023, 12(5), 714; https://doi.org/10.3390/pathogens12050714 - 13 May 2023
Cited by 5 | Viewed by 3041
Abstract
Controlling the abundance of blacklegged ticks is considered the foundation for the prevention of human exposure to pathogens transmitted by these vectors in eastern North America. The use of broadcast or host-targeted acaricides is generally found to be effective at reducing the local [...] Read more.
Controlling the abundance of blacklegged ticks is considered the foundation for the prevention of human exposure to pathogens transmitted by these vectors in eastern North America. The use of broadcast or host-targeted acaricides is generally found to be effective at reducing the local abundance of ticks. However, studies that incorporate randomization, placebo controls, and masking, i.e., “blinding”, generally find lower efficacy. The few studies that include measurements of human–tick encounters and cases of tickborne disease have not shown impacts of acaricidal treatments. We compile literature on relevant studies from northeastern North America to address possible causes for discrepancies in study outcomes and suggest possible mechanisms that could underlie the diminished efficacy of tick control in reducing cases of tickborne disease in people. Full article
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0 pages, 417 KiB  
Review
Heartbreaking Decisions: The Dogma and Uncertainties of Antimicrobial Therapy in Infective Endocarditis
by Jennifer L. Adema, Aileen Ahiskali, Madiha Fida, Krutika Mediwala Hornback, Ryan W. Stevens and Christina G. Rivera
Pathogens 2023, 12(5), 703; https://doi.org/10.3390/pathogens12050703 - 12 May 2023
Cited by 3 | Viewed by 3858
Abstract
Infective endocarditis (IE) is a rare but increasingly prevalent disease with high morbidity and mortality, requiring antimicrobials and at times surgical intervention. Through the decades of healthcare professionals’ experience with managing IE, certain dogmas and uncertainties have arisen around its pharmacotherapy. The introduction [...] Read more.
Infective endocarditis (IE) is a rare but increasingly prevalent disease with high morbidity and mortality, requiring antimicrobials and at times surgical intervention. Through the decades of healthcare professionals’ experience with managing IE, certain dogmas and uncertainties have arisen around its pharmacotherapy. The introduction of new antimicrobials and novel combinations are exciting developments but also further complicate IE treatment choices. In this review, we provide and evaluate the relevant evidence focused around contemporary debates in IE treatment pharmacotherapy, including beta-lactam choice in MSSA IE, combination therapies (aminoglycosides, ceftaroline), the use of oral antimicrobials, the role of rifamycins, and long-acting lipoglycopeptides. Full article
(This article belongs to the Special Issue Updates in Infective Endocarditis)
14 pages, 2611 KiB  
Article
Characterisation of a Staphylococcus aureus Isolate Carrying Phage-Borne Enterotoxin E from a European Badger (Meles meles)
by Sindy Burgold-Voigt, Stefan Monecke, Anne Busch, Herbert Bocklisch, Sascha D. Braun, Celia Diezel, Helmut Hotzel, Elisabeth M. Liebler-Tenorio, Elke Müller, Martin Reinicke, Annett Reissig, Antje Ruppelt-Lorz and Ralf Ehricht
Pathogens 2023, 12(5), 704; https://doi.org/10.3390/pathogens12050704 - 12 May 2023
Cited by 3 | Viewed by 2375
Abstract
Staphylococcus (S.) aureus colonizes up to 30% of all humans and can occasionally cause serious infections. It is not restricted to humans as it can also often be found in livestock and wildlife. Recent studies have shown that wildlife strains of [...] Read more.
Staphylococcus (S.) aureus colonizes up to 30% of all humans and can occasionally cause serious infections. It is not restricted to humans as it can also often be found in livestock and wildlife. Recent studies have shown that wildlife strains of S. aureus usually belong to other clonal complexes than human strains and that they might differ significantly with regard to the prevalence of genes encoding antimicrobial resistance properties and virulence factors. Here, we describe a strain of S. aureus isolated from a European badger (Meles meles). For molecular characterisation, DNA microarray-based technology was combined with various next-generation sequencing (NGS) methods. Bacteriophages from this isolate were induced with Mitomycin C and characterized in detail by transmission electron microscopy (TEM) and NGS. The S. aureus isolate belonged to ST425 and had a novel spa repeat sequence (t20845). It did not carry any resistance genes. The uncommon enterotoxin gene see was detected in one of its three temperate bacteriophages. It was possible to demonstrate the induction of all three prophages, although only one of them was expected to be capable of excision based on its carriage of the excisionase gene xis. All three bacteriophages belonged to the family Siphoviridae. Minor differences in size and shape of their heads were noted in TEM images. The results highlight the ability of S. aureus to colonize or infect different host species successfully, which can be attributed to a variety of virulence factors on mobile genetic elements, such as bacteriophages. As shown in the strain described herein, temperate bacteriophages not only contribute to the fitness of their staphylococcal host by transferring virulence factors, but also increase mobility among themselves by sharing genes for excision and mobilization with other prophages. Full article
(This article belongs to the Special Issue Surveillance of Zoonotic Pathogens Carried by Wildlife)
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10 pages, 626 KiB  
Article
Use of In-Clinic Diagnostic Kits for the Detection of Seropositivity to Leishmania infantum and Other Major Vector-Borne Pathogens in Healthy Dogs
by Simone Morelli, Anastasia Diakou, Antonio Frangipane di Regalbono, Mariasole Colombo, Giulia Simonato, Angela Di Cesare, Alessandra Passarelli, Carlo Pezzuto, Zoe Tzitzoudi, Alessandra Barlaam, Melissa Beall, Ramaswamy Chandrashekar, Nikola Pantchev and Donato Traversa
Pathogens 2023, 12(5), 696; https://doi.org/10.3390/pathogens12050696 - 11 May 2023
Cited by 3 | Viewed by 2275
Abstract
Canine Vector-Borne Diseases (CVBDs) are widespread in Europe and enzootic in many other countries. Though severe illnesses may occur, dogs living in enzootic areas often show vague or no clinical signs of CVBDs. Undiagnosed infections/co-infections in subclinically infected animals favor the spread of [...] Read more.
Canine Vector-Borne Diseases (CVBDs) are widespread in Europe and enzootic in many other countries. Though severe illnesses may occur, dogs living in enzootic areas often show vague or no clinical signs of CVBDs. Undiagnosed infections/co-infections in subclinically infected animals favor the spread of CVBDs and increase the risk of transmission to other animals and, in some cases, humans. This study has evaluated the exposure of dogs living in key enzootic countries, i.e., Italy and Greece, to major CVBDs via the use of in-clinic diagnostic kits. Overall, 300 privately owned dogs without/with single mild clinical signs living in different regions of Italy (n. 150) and Greece (n. 150) were included in the study. As part of a clinical examination, a blood sample was collected from each dog and subjected to two serological rapid tests, i.e., the SNAP® 4Dx®Plus (IDEXX Laboratories Inc.) for the detection of antibodies against Ehrlichia spp., Anaplasma spp., Borrelia burgdorferi s.l. and Dirofilaria immitis antigen and the SNAP® Leishmania (IDEXX Laboratories Inc.) for the detection of antibodies against Leishmania infantum. In all, 51 dogs (17%; 95% CI 12.9–21.7) were seropositive to at least 1 pathogen, i.e., 4 in Italy (2.7%; 95% CI 1.4–13.1) and 47 in Greece (31.3%; 95% CI 24–39.4). Dirofilaria immitis antigens were found in 39 dogs (13%; 95% CI 9.4–17.3), while antibodies against Ehrlichia, Anaplasma and Leishmania were detected in 25 (8.3%; 95% CI 5.5–12.1), 8 (2.7%; 95% CI 1.2–5.2) and 5 (1.7%; 95% CI 0.5–3.8) dogs, respectively. None of the dogs tested seropositive for B. burgdorferi s.l. Statistical analyses were performed to evaluate associations between exposure to CVBDs and possible risk factors. The present results indicate that dogs living in enzootic areas may be seropositive for one or more CVBDs in absence of clinical signs. Rapid kits are among first line tools for the detection of CVBDs in clinical settings, as they are cost-effective, straightforward and quick to use. Also, in-clinic tests used herein allowed detection of co-exposure to CVBDs investigated. Full article
(This article belongs to the Collection Pathology and Parasitic Diseases of Animals)
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12 pages, 2309 KiB  
Article
Identification of Trichomonas vaginalis 5-Nitroimidazole Resistance Targets
by Keonte J. Graves, Colin Reily, Hemant K. Tiwari, Vinodh Srinivasasainagendra, William Evan Secor, Jan Novak and Christina A. Muzny
Pathogens 2023, 12(5), 692; https://doi.org/10.3390/pathogens12050692 - 10 May 2023
Cited by 1 | Viewed by 2464
Abstract
Trichomonas vaginalis is the most common non-viral sexually transmitted infection. 5-nitroimidazoles are the only FDA-approved medications for T. vaginalis treatment. However, 5-nitroimidazole resistance has been increasingly recognized and may occur in up to 10% of infections. We aimed to delineate mechanisms of T. [...] Read more.
Trichomonas vaginalis is the most common non-viral sexually transmitted infection. 5-nitroimidazoles are the only FDA-approved medications for T. vaginalis treatment. However, 5-nitroimidazole resistance has been increasingly recognized and may occur in up to 10% of infections. We aimed to delineate mechanisms of T. vaginalis resistance using transcriptome profiling of metronidazole (MTZ)-resistant and sensitive T. vaginalis clinical isolates. In vitro, 5-nitroimidazole susceptibility testing was performed to determine minimum lethal concentrations (MLCs) for T. vaginalis isolates obtained from women who had failed treatment (n = 4) or were successfully cured (n = 4). RNA sequencing, bioinformatics, and biostatistical analyses were performed to identify differentially expressed genes (DEGs) in the MTZ-resistant vs. sensitive T. vaginalis isolates. RNA sequencing identified 304 DEGs, 134 upregulated genes and 170 downregulated genes in the resistant isolates. Future studies with more T. vaginalis isolates with a broad range of MLCs are needed to determine which genes may represent the best alternative targets in drug-resistant strains. Full article
(This article belongs to the Special Issue Trichomonas vaginalis Infection)
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17 pages, 4138 KiB  
Article
Assessing the Operational Feasibility of Integrating Point-of-Care G6PD Testing into Plasmodium vivax Malaria Management in Vietnam
by Emily Gerth-Guyette, Huyen Thanh Nguyen, Spike Nowak, Nga Thu Hoang, Đặng Thị Tuyết Mai, Vũ Thị Sang, Nguyễn Đức Long, Mercy Mvundura, Nhu Nguyen, Gonzalo J. Domingo and Bùi Quang Phúc
Pathogens 2023, 12(5), 689; https://doi.org/10.3390/pathogens12050689 - 8 May 2023
Cited by 5 | Viewed by 2319
Abstract
Plasmodium vivax cases represent more than 50% of a diminishing malaria case load in Vietnam. Safe and effective radical cure strategies could support malaria elimination by 2030. This study investigated the operational feasibility of introducing point-of-care quantitative glucose-6-phosphate dehydrogenase (G6PD) testing into malaria [...] Read more.
Plasmodium vivax cases represent more than 50% of a diminishing malaria case load in Vietnam. Safe and effective radical cure strategies could support malaria elimination by 2030. This study investigated the operational feasibility of introducing point-of-care quantitative glucose-6-phosphate dehydrogenase (G6PD) testing into malaria case management practices. A prospective interventional study was conducted at nine district hospitals and commune health stations in Binh Phuoc and Gia Lai provinces in Vietnam over the period of October 2020 to October 2021. The STANDARD™ G6PD Test (SD Biosensor, Seoul, Republic of Korea) was incorporated to inform P. vivax case management. Case management data and patient and health care provider (HCP) perspectives, as well as detailed cost data were collected. The G6PD test results were interpreted correctly by HCP and the treatment algorithm was adhered to for the majority of patients. One HCP consistently ran the test incorrectly, which was identified during the monitoring and resulted in provision of refresher training and updating of training materials and patient retesting. There was wide acceptability of the intervention among patients and HCP albeit with opportunities to improve the counseling materials. Increasing the number of facilities to which the test was deployed and decreases in the malaria cases resulted in higher per patient cost for incorporating G6PD testing into the system. Commodity costs can be reduced by using the 10-unit kits compared to the 25 unit kits, particularly when the case loads are low. These results demonstrate intervention feasibility while also highlighting specific challenges for a country approaching malaria elimination. Full article
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11 pages, 1103 KiB  
Review
The Role of Parasitoid Wasps, Ixodiphagus spp. (Hymenoptera: Encyrtidae), in Tick Control
by Rafael Antonio Nascimento Ramos, Lucia Oliveira de Macedo, Marcos Antônio Bezerra-Santos, Gílcia Aparecida de Carvalho, Guilherme Gomes Verocai and Domenico Otranto
Pathogens 2023, 12(5), 676; https://doi.org/10.3390/pathogens12050676 - 3 May 2023
Cited by 4 | Viewed by 2480
Abstract
Species of Ixodiphagus (Hymenoptera: Encyrtidae) are parasitoid wasps whose immature forms develop inside ixodid and argasid ticks (Acari: Ixodida). Following oviposition by adult female wasps into the idiosoma of ticks, larvae hatch and start feeding on their internal contents, eventually emerging as adult [...] Read more.
Species of Ixodiphagus (Hymenoptera: Encyrtidae) are parasitoid wasps whose immature forms develop inside ixodid and argasid ticks (Acari: Ixodida). Following oviposition by adult female wasps into the idiosoma of ticks, larvae hatch and start feeding on their internal contents, eventually emerging as adult wasps from the body of the dead ticks. Species of Ixodiphagus have been reported as parasitoids of 21 species of ticks distributed across 7 genera. There are at least ten species described in the genus, with Ixodiphagus hookeri being the most studied as an agent for biological control of ticks. Although attempts of tick control by means of this parasitoid largely failed, in a small-scale study 150,000 specimens of I. hookeri were released over a 1-year period in a pasture where a small cattle population was kept, resulting in an overall reduction in the number of Amblyomma variegatum ticks per animal. This review discusses current scientific information about Ixodiphagus spp., focusing on the role of this parasitoid in the control of ticks. The interactions between these wasps and the ticks’ population are also discussed, focusing on the many biological and logistical challenges, with limitations of this control method for reducing tick populations under natural conditions. Full article
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19 pages, 3217 KiB  
Article
Recurrent Loss of Macrodomain Activity in Host Immunity and Viral Proteins
by Sofia E. Delgado-Rodriguez, Andrew P. Ryan and Matthew D. Daugherty
Pathogens 2023, 12(5), 674; https://doi.org/10.3390/pathogens12050674 - 3 May 2023
Cited by 9 | Viewed by 3048
Abstract
Protein post-translational modifications (PTMs) are an important battleground in the evolutionary arms races that are waged between the host innate immune system and viruses. One such PTM, ADP-ribosylation, has recently emerged as an important mediator of host antiviral immunity. Important for the host–virus [...] Read more.
Protein post-translational modifications (PTMs) are an important battleground in the evolutionary arms races that are waged between the host innate immune system and viruses. One such PTM, ADP-ribosylation, has recently emerged as an important mediator of host antiviral immunity. Important for the host–virus conflict over this PTM is the addition of ADP-ribose by PARP proteins and removal of ADP-ribose by macrodomain-containing proteins. Interestingly, several host proteins, known as macroPARPs, contain macrodomains as well as a PARP domain, and these proteins are both important for the host antiviral immune response and evolving under very strong positive (diversifying) evolutionary selection. In addition, several viruses, including alphaviruses and coronaviruses, encode one or more macrodomains. Despite the presence of the conserved macrodomain fold, the enzymatic activity of many of these proteins has not been characterized. Here, we perform evolutionary and functional analyses to characterize the activity of macroPARP and viral macrodomains. We trace the evolutionary history of macroPARPs in metazoans and show that PARP9 and PARP14 contain a single active macrodomain, whereas PARP15 contains none. Interestingly, we also reveal several independent losses of macrodomain enzymatic activity within mammalian PARP14, including in the bat, ungulate, and carnivore lineages. Similar to macroPARPs, coronaviruses contain up to three macrodomains, with only the first displaying catalytic activity. Intriguingly, we also reveal the recurrent loss of macrodomain activity within the alphavirus group of viruses, including enzymatic loss in insect-specific alphaviruses as well as independent enzymatic losses in two human-infecting viruses. Together, our evolutionary and functional data reveal an unexpected turnover in macrodomain activity in both host antiviral proteins and viral proteins. Full article
(This article belongs to the Special Issue ADP-Ribosylation in Pathogens)
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9 pages, 1379 KiB  
Article
Hepatitis E Virus (HEV) Infection in Hemodialysis Patients: A Multicenter Epidemiological Cohort Study in North-Eastern Greece
by Dionysios Kogias, Aikaterini Skeva, Andreas Smyrlis, Efthymia Mourvati, Konstantinia Kantartzi, Gioulia Romanidou, Maria Kalientzidou, Vasiliki Rekari, Eleni Konstantinidou, Parthena Kiorteve, Ioannis Paroglou, Vasileios Papadopoulos, Theocharis Konstantinidis, Maria Panopoulou and Konstantinos Mimidis
Pathogens 2023, 12(5), 667; https://doi.org/10.3390/pathogens12050667 - 30 Apr 2023
Cited by 2 | Viewed by 1981
Abstract
Hepatitis E virus (HEV), a common cause of viral hepatitis in developing countries, is mainly transmitted via the fecal–oral route, but also may be a prevalent hospital-transmitted agent among patients on regular hemodialysis due to parenteral transmission. Previous epidemiological studies among hemodialysis patients [...] Read more.
Hepatitis E virus (HEV), a common cause of viral hepatitis in developing countries, is mainly transmitted via the fecal–oral route, but also may be a prevalent hospital-transmitted agent among patients on regular hemodialysis due to parenteral transmission. Previous epidemiological studies among hemodialysis patients in Greece, using different diagnostic techniques, gave conflicting results. Τhe present study aimed to measure the exposure rate of hemodialysis patients of north-eastern Greece to HEV by estimating the overall seroprevalence, and to identify potential risk factors. Serum samples from all patients attending the hemodialysis centers of north-eastern Greece (n = 6) were tested for the presence of anti-HEV IgG antibodies using a modern and sensitive ELISA (Enzyme-linked Immunosorbent Assay) technique (Wantai). In total, 42 out of 405 hemodialysis patients were positive for anti-HEV IgG (10.4%), while all samples were negative for HEV RNA when tested using nested RT-PCR. HEV seropositivity among hemodialysis patients was significantly associated with area of residence and contact with specific animals (pork, deer). No association was found with religion, gender distribution and hemodialysis duration. This study showed an increased seroprevalence of HEV among hemodialysis patients in Greece. Agricultural or livestock occupation and place of residence seem to be independent factors that increase the risk of HEV infection. In conclusion, HEV infection calls for the regular screening of hemodialysis patients regardless of the hemodialysis duration or clinical symptoms. Full article
(This article belongs to the Special Issue Pathogens in 2023)
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21 pages, 2392 KiB  
Review
A Review of the Current Status of G6PD Deficiency Testing to Guide Radical Cure Treatment for Vivax Malaria
by Arkasha Sadhewa, Sarah Cassidy-Seyoum, Sanjaya Acharya, Angela Devine, Ric N. Price, Muthoni Mwaura, Kamala Thriemer and Benedikt Ley
Pathogens 2023, 12(5), 650; https://doi.org/10.3390/pathogens12050650 - 27 Apr 2023
Cited by 9 | Viewed by 5700
Abstract
Plasmodium vivax malaria continues to cause a significant burden of disease in the Asia-Pacific, the Horn of Africa, and the Americas. In addition to schizontocidal treatment, the 8-aminoquinoline drugs are crucial for the complete removal of the parasite from the human host (radical [...] Read more.
Plasmodium vivax malaria continues to cause a significant burden of disease in the Asia-Pacific, the Horn of Africa, and the Americas. In addition to schizontocidal treatment, the 8-aminoquinoline drugs are crucial for the complete removal of the parasite from the human host (radical cure). While well tolerated in most recipients, 8-aminoquinolines can cause severe haemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficient patients. G6PD deficiency is one of the most common enzymopathies worldwide; therefore, the WHO recommends routine testing to guide 8-aminoquinoline based treatment for vivax malaria whenever possible. In practice, this is not yet implemented in most malaria endemic countries. This review provides an update of the characteristics of the most used G6PD diagnostics. We describe the current state of policy and implementation of routine point-of-care G6PD testing in malaria endemic countries and highlight key knowledge gaps that hinder broader implementation. Identified challenges include optimal training of health facility staff on point-of-care diagnostics, quality control of novel G6PD diagnostics, and culturally appropriate information and communication with affected communities around G6PD deficiency and implications for treatment. Full article
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17 pages, 2005 KiB  
Review
Urinary Tract Infections: The Current Scenario and Future Prospects
by Giuseppe Mancuso, Angelina Midiri, Elisabetta Gerace, Maria Marra, Sebastiana Zummo and Carmelo Biondo
Pathogens 2023, 12(4), 623; https://doi.org/10.3390/pathogens12040623 - 20 Apr 2023
Cited by 54 | Viewed by 25701
Abstract
Urinary tract infections (UTIs) are among the most common bacterial infections worldwide, occurring in both community and healthcare settings. Although the clinical symptoms of UTIs are heterogeneous and range from uncomplicated (uUTIs) to complicated (cUTIs), most UTIs are usually treated empirically. Bacteria are [...] Read more.
Urinary tract infections (UTIs) are among the most common bacterial infections worldwide, occurring in both community and healthcare settings. Although the clinical symptoms of UTIs are heterogeneous and range from uncomplicated (uUTIs) to complicated (cUTIs), most UTIs are usually treated empirically. Bacteria are the main causative agents of these infections, although more rarely, other microorganisms, such as fungi and some viruses, have been reported to be responsible for UTIs. Uropathogenic Escherichia coli (UPEC) is the most common causative agent for both uUTIs and cUTIs, followed by other pathogenic microorganisms, such as Klebsiella pneumoniae, Proteus mirabilis, Enterococcus faecalis, and Staphylococcus spp. In addition, the incidence of UTIs caused by multidrug resistance (MDR) is increasing, resulting in a significant increase in the spread of antibiotic resistance and the economic burden of these infections. Here, we discuss the various factors associated with UTIs, including the mechanisms of pathogenicity related to the bacteria that cause UTIs and the emergence of increasing resistance in UTI pathogens. Full article
(This article belongs to the Special Issue Pathogens in 2023)
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14 pages, 1093 KiB  
Review
Clinical Evidence for the Use of Octenidine Dihydrochloride to Prevent Healthcare-Associated Infections and Decrease Staphylococcus aureus Carriage or Transmission—A Review
by Robin Köck, Luisa Denkel, Andrea T. Feßler, Rudolf Eicker, Alexander Mellmann, Stefan Schwarz, Christine Geffers, Nils-Olaf Hübner and Rasmus Leistner
Pathogens 2023, 12(4), 612; https://doi.org/10.3390/pathogens12040612 - 18 Apr 2023
Cited by 3 | Viewed by 2662
Abstract
Background: The antiseptic agent octenidine dihydrochloride (OCT) is used for skin preparation, for Staphylococcus aureus decolonization, and within bundles for the prevention of catheter-related or surgical site infections (SSIs). Here, we review the evidence for the effects of OCT from clinical studies. Methods: [...] Read more.
Background: The antiseptic agent octenidine dihydrochloride (OCT) is used for skin preparation, for Staphylococcus aureus decolonization, and within bundles for the prevention of catheter-related or surgical site infections (SSIs). Here, we review the evidence for the effects of OCT from clinical studies. Methods: Review of studies published in the Medline, Scopus, and Cochrane databases until August 2022, performed in clinical settings and reporting on effects of OCT on S. aureus carriage/transmission, SSI prevention, and prevention of intensive care unit (ICU)-related or catheter-related bloodstream and insertion site infections. Results: We included 31 articles. The success of S. aureus decolonization with OCT-containing therapies ranged between 6 and 87%. Single studies demonstrated that OCT application led to a reduction in S. aureus infections, acquisition, and carriage. No study compared OCT for skin preparation before surgical interventions to other antiseptics. Weak evidence for the use of OCT for pre-operative washing was found in orthopedic and cardiac surgery, if combined with other topical measures. Mostly, studies did not demonstrate that daily OCT bathing reduced ICU-/catheter-related bloodstream infections with one exception. Conclusions: There is a need to perform studies assessing the clinical use of OCT compared with other antiseptics with respect to its effectiveness to prevent nosocomial infections. Full article
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23 pages, 831 KiB  
Review
The Humanized Mouse Model: What Added Value Does It Offer for HIV Research?
by Luca Baroncini, Simon Bredl, Kadzioch P. Nicole and Roberto F. Speck
Pathogens 2023, 12(4), 608; https://doi.org/10.3390/pathogens12040608 - 17 Apr 2023
Cited by 5 | Viewed by 4173
Abstract
In the early 2000s, novel humanized mouse models based on the transplantation of human hematopoietic stem and progenitor cells (HSPCs) into immunocompromised mice were introduced (hu mice). The human HSPCs gave rise to a lymphoid system of human origin. The HIV research community [...] Read more.
In the early 2000s, novel humanized mouse models based on the transplantation of human hematopoietic stem and progenitor cells (HSPCs) into immunocompromised mice were introduced (hu mice). The human HSPCs gave rise to a lymphoid system of human origin. The HIV research community has greatly benefitted from these hu mice. Since human immunodeficiency virus (HIV) type 1 infection results in a high-titer disseminated HIV infection, hu mice have been of great value for all types of HIV research from pathogenesis to novel therapies. Since the first description of this new generation of hu mice, great efforts have been expended to improve humanization by creating other immunodeficient mouse models or supplementing mice with human transgenes to improve human engraftment. Many labs have their own customized hu mouse models, making comparisons quite difficult. Here, we discuss the different hu mouse models in the context of specific research questions in order to define which characteristics should be considered when determining which hu mouse model is appropriate for the question posed. We strongly believe that researchers must first define their research question and then determine whether a hu mouse model exists, allowing the research question to be studied. Full article
(This article belongs to the Special Issue Animal Models for Human Viruses)
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9 pages, 478 KiB  
Article
Debridement, Antibiotic Pearls, and Retention of the Implant (DAPRI) in the Treatment of Early Periprosthetic Joint Infections: A Consecutive Series
by Pier Francesco Indelli, Stefano Ghirardelli, Pieralberto Valpiana, Lorenzo Bini, Michele Festini and Ferdinando Iannotti
Pathogens 2023, 12(4), 605; https://doi.org/10.3390/pathogens12040605 - 16 Apr 2023
Cited by 9 | Viewed by 2975
Abstract
Introduction: Periprosthetic joint infections (PJI) represent a devastating consequence following total joint arthroplasty (TJA). In this study, the authors describe a modified surgical technique developed to enhance the classical irrigation and debridement procedure (DAIR) to improve the possibilities of retaining an acutely infected [...] Read more.
Introduction: Periprosthetic joint infections (PJI) represent a devastating consequence following total joint arthroplasty (TJA). In this study, the authors describe a modified surgical technique developed to enhance the classical irrigation and debridement procedure (DAIR) to improve the possibilities of retaining an acutely infected TJA. Materials and Methods: This technique, debridement antibiotic pearls and retention of the implant (DAPRI), aims to remove the intra-articular biofilm allowing a higher and prolonged local antibiotic concentration by using calcium sulphate antibiotic-added beads in a setting of acute (<4 weeks from symptoms onset) PJI with pathogen identification. The combination of three different surgical techniques (tumor-like synovectomy, argon beam/acetic acid application and chlorhexidine gluconate brushing) aims to remove the bacterial biofilm from the implant without explanting the original hardware. Results: In total, 62 patients met the acute infection criteria (<4 weeks of symptoms); there were 57 males and five females. The patients’ average age at the time of treatment was 71 years (62–77) and the average BMI was 37 kg/m2. The micro-organism, always identified through synovial fluid analysis (culture, multiplex PCR or Next Generation Sequencing), was an aerobic Gram + in 76% (S. Coag-Neg 41%; S. aureus 16%), Gram—in 10% (E. coli 4%) and anaerobic Gram + in 4%. The DAPRI treatment was performed at an average of 3 days from symptoms onset (1–7 days). All patients underwent a 12-week course of post-operative antibiotic therapy (6 weeks I.V. and 6 weeks oral). All patients were available at the 2-year minimum FU (24–84 months). A total of 48 (77.5%) patients were infection-free at the final FU, while 14 patients underwent 2-stage revision for PJI recurrence. In total, four patients (6.4%) had a prolonged drainage from the wound after placement of the calcium sulphate beads. Conclusions: This study suggests that the DAPRI technique could represent a valid alternative to the classic DAIR procedure. The current authors do not recommend this procedure outside of the main inclusive criteria (acute scenario micro-organism identification). Full article
(This article belongs to the Section Bacterial Pathogens)
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12 pages, 1141 KiB  
Review
Antimicrobial Effects of Lactoferrin against Helicobacter pylori Infection
by Ichiro Imoto, Taro Yasuma, Corina N. D’Alessandro-Gabazza, Satoko Oka, Moriharu Misaki, Noriyuki Horiki and Esteban C. Gabazza
Pathogens 2023, 12(4), 599; https://doi.org/10.3390/pathogens12040599 - 14 Apr 2023
Cited by 6 | Viewed by 4601
Abstract
Helicobacter (H.) pylori is the primary causative agent of various gastroduodenal diseases. H. pylori is an adapted microorganism that has evolved to survive in the acidic conditions of the human stomach, possessing a natural strategy for colonizing harsh environments. Despite the [...] Read more.
Helicobacter (H.) pylori is the primary causative agent of various gastroduodenal diseases. H. pylori is an adapted microorganism that has evolved to survive in the acidic conditions of the human stomach, possessing a natural strategy for colonizing harsh environments. Despite the implementation of various eradication regimens worldwide, the eradication rate of H. pylori has decreased to less than 80% in recent years due to the emergence of antibiotic-resistant strains. This has posed a significant challenge in treating H. pylori infection, as antibiotic resistance and side effects have become increasingly problematic. Lactoferrin, a member of the transferrin family, is an iron-binding protein with antioxidant, antibacterial, antiviral, and anti-inflammatory properties that promote human health. The concentrations of lactoferrin in the gastric juice and mucosa significantly increase during H. pylori infection and are strongly correlated with the severity of gastric mucosal inflammation. Numerous researchers have studied the antimicrobial properties of lactoferrin both in vitro and in vivo. In addition, recent studies have investigated the addition of oral lactoferrin supplementation to H. pylori eradication therapy, even though monotherapy with lactoferrin does not eradicate the microorganism. In this article, we reviewed the survival strategy of H. pylori to evade the antimicrobial activity of human lactoferrin and explore the potential of lactoferrin in H. pylori eradication therapy. Full article
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15 pages, 567 KiB  
Article
Uncovering the Yeast Diversity in the Female Genital Tract: An Exploration of Spatial Distribution and Antifungal Resistance
by Mariana Zagalo Fernandes, Cátia Filipa Caetano, Carlos Gaspar, Ana Sofia Oliveira, Rita Palmeira-de-Oliveira, José Martinez-de-Oliveira, Joana Rolo and Ana Palmeira-de-Oliveira
Pathogens 2023, 12(4), 595; https://doi.org/10.3390/pathogens12040595 - 14 Apr 2023
Cited by 5 | Viewed by 3304
Abstract
Candida albicans is the leading cause of vulvovaginal yeast infections; however, other species are becoming relevant in this niche. The spatial distribution of these fungi in the female genital tract remains poorly understood. In this study, swab samples were collected from 33 patients, [...] Read more.
Candida albicans is the leading cause of vulvovaginal yeast infections; however, other species are becoming relevant in this niche. The spatial distribution of these fungi in the female genital tract remains poorly understood. In this study, swab samples were collected from 33 patients, first from the anterior vulva and then from the upper third and right lateral wall of the vagina: 16 were with symptoms of vulvovaginal candidiasis and 17 were without characteristic symptoms; furthermore, the genus and species of each isolate were identified. In vitro susceptibility testing for fluconazole and clotrimazole was performed for all isolates. Candida albicans was the most common species (63.6%), followed by Rhodotorula spp. (51.5%), and then Candida parapsilosis (15.2%). Rhodotorula spp. and C. parapsilosis were more commonly associated with colonization, and C. albicans with infection. Rhodotorula spp. isolates presented a low susceptibility to fluconazole, with the MIC ranging from 32 to >64 µg/mL. Differences in susceptibility to fluconazole and clotrimazole between the pairs of vaginal and vulvar isolates were found for Candida albicans, Rhodotorula spp., and Nakaseomyces glabratus. The results suggest that different niches may impact the susceptibility profiles of the isolates, as well as their different clinical behaviors. Full article
(This article belongs to the Special Issue Opportunistic Fungal Infections)
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8 pages, 237 KiB  
Opinion
Common Neurologic Features of Lyme Disease That May Present to a Rheumatologist
by Swati Govil, Eugenio Capitle, Alexandra Lacqua, Reena Khianey, P.K. Coyle and Steven E. Schutzer
Pathogens 2023, 12(4), 576; https://doi.org/10.3390/pathogens12040576 - 9 Apr 2023
Cited by 5 | Viewed by 2894
Abstract
Lyme disease, caused by Borrelia burgdorferi (Bb) infection, has a broad spectrum of clinical manifestations and severity. Patients with possible Lyme disease may seek out or be referred to rheumatologists. Today, the most common reason to engage a rheumatologist is due to complaints [...] Read more.
Lyme disease, caused by Borrelia burgdorferi (Bb) infection, has a broad spectrum of clinical manifestations and severity. Patients with possible Lyme disease may seek out or be referred to rheumatologists. Today, the most common reason to engage a rheumatologist is due to complaints of arthralgia. After skin, neurologic manifestations of Lyme disease are now among the most common. Therefore, it is important for rheumatologists to be aware of clues that suggest neurologic Lyme disease and prompt help from a neurologist experienced with Lyme disease. Full article
12 pages, 6616 KiB  
Article
Update on the First Finding of the Rat Lungworm, Angiostrongylus cantonensis, in Rattus spp. in Continental Europe, Valencia, Spain, 2022
by María Teresa Galán-Puchades, Mercedes Gómez-Samblás, Antonio Osuna, Sandra Sáez-Durán, Rubén Bueno-Marí and Màrius V. Fuentes
Pathogens 2023, 12(4), 567; https://doi.org/10.3390/pathogens12040567 - 6 Apr 2023
Cited by 8 | Viewed by 3208
Abstract
The rat lungworm, Angiostrongylus cantonensis, is an emerging parasite that can cause eosinophilic meningitis in humans. Over the past 60 years, the worm has greatly expanded its original Asian distribution to most tropical and subtropical areas of the world, mostly by traveling [...] Read more.
The rat lungworm, Angiostrongylus cantonensis, is an emerging parasite that can cause eosinophilic meningitis in humans. Over the past 60 years, the worm has greatly expanded its original Asian distribution to most tropical and subtropical areas of the world, mostly by traveling on ships with its definitive hosts, rats. Angiostrongylus cantonensis was recently found for the first time in Continental Europe, specifically in 3 (2 Rattus norvegicus and 1 Rattus rattus) out of 27 rats trapped in the sewer system of the city of Valencia, Spain. Updating the investigation, the parasite has subsequently been found in 8 (5 R. norvegicus and 3 R. rattus) out of 94 rats analyzed. The highest prevalence of infection (20%) was obtained in rats trapped in the orchards that surround the city, where both snails and slugs (intermediate hosts) abound, and where vegetables consumed in Valencia, other parts of Spain, and abroad, are produced. The presence of the parasite in rats does not necessarily mean that the disease it causes becomes a relevant public health concern since it strongly depends on the food habits of the population at risk. If proper precautions are taken, the risk of acquiring neuroangiostrongylosis should be minimal. Full article
(This article belongs to the Special Issue Advances in Parasitic Diseases)
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21 pages, 6939 KiB  
Systematic Review
Relevant Brachycera (Excluding Oestroidea) for Horses in Veterinary Medicine: A Systematic Review
by Vicky Frisch, Hans-Peter Fuehrer and Jessika-M. V. Cavalleri
Pathogens 2023, 12(4), 568; https://doi.org/10.3390/pathogens12040568 - 6 Apr 2023
Cited by 2 | Viewed by 2068
Abstract
In equine stables and their surroundings, a large number of insects are present that can be a nuisance to their equine hosts. Previous studies about dipterans transmitting infectious agents to Equidae have largely focused on Nematocera. For the preparation of this systematic review, [...] Read more.
In equine stables and their surroundings, a large number of insects are present that can be a nuisance to their equine hosts. Previous studies about dipterans transmitting infectious agents to Equidae have largely focused on Nematocera. For the preparation of this systematic review, the existing literature (until February 2022) was systematically screened for various infectious agents transmitted to Equidae via insects of the suborder Brachycera, including Tabanidae, Muscidae, Glossinidae and Hippoboscidae, acting as pests or potential vectors. The PRISMA statement 2020 (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for systematic reviews were followed. The two concepts, Brachycera and Equidae, were combined for the search that was carried out in three languages (English, German and French) using four different search engines. In total, 38 articles investigating Brachycera as vectors for viral, bacterial and parasitic infections or as pests of equids were identified. Only 7 of the 14 investigated pathogens in the 38 reports extracted from the literature were shown to be transmitted by Brachycera. This review clearly shows that further studies are needed to investigate the role of Brachycera as vectors for pathogens relevant to equine health. Full article
(This article belongs to the Special Issue Advances in Parasitic Diseases—Second Edition)
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22 pages, 5347 KiB  
Article
Rift Valley Fever Virus Primes Immune Responses in Aedes aegypti Cells
by Mathilde Laureti, Rui-Xue Lee, Amelia Bennett, Lucas Aladar Wilson, Victoria Elena Sy, Alain Kohl and Isabelle Dietrich
Pathogens 2023, 12(4), 563; https://doi.org/10.3390/pathogens12040563 - 6 Apr 2023
Cited by 4 | Viewed by 3836
Abstract
The ongoing global emergence of arthropod-borne (arbo) viruses has accelerated research into the interactions of these viruses with the immune systems of their vectors. Only limited information exists on how bunyaviruses, such as Rift Valley fever virus (RVFV), are sensed by mosquito immunity [...] Read more.
The ongoing global emergence of arthropod-borne (arbo) viruses has accelerated research into the interactions of these viruses with the immune systems of their vectors. Only limited information exists on how bunyaviruses, such as Rift Valley fever virus (RVFV), are sensed by mosquito immunity or escape detection. RVFV is a zoonotic phlebovirus (Bunyavirales; Phenuiviridae) of veterinary and human public health and economic importance. We have shown that the infection of mosquitoes with RVFV triggers the activation of RNA interference pathways, which moderately restrict viral replication. Here, we aimed to better understand the interactions between RVFV and other vector immune signaling pathways that might influence RVFV replication and transmission. For this, we used the immunocompetent Aedes aegypti Aag2 cell line as a model. We found that bacteria-induced immune responses restricted RVFV replication. However, virus infection alone did not alter the gene expression levels of immune effectors. Instead, it resulted in the marked enhancement of immune responses to subsequent bacterial stimulation. The gene expression levels of several mosquito immune pattern recognition receptors were altered by RVFV infection, which may contribute to this immune priming. Our findings imply that there is a complex interplay between RVFV and mosquito immunity that could be targeted in disease prevention strategies. Full article
(This article belongs to the Special Issue Pathogens in 2023)
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12 pages, 1186 KiB  
Article
A U.S. Isolate of Theileria orientalis Ikeda Is Not Transstadially Transmitted to Cattle by Rhipicephalus microplus
by Cynthia K. Onzere, David R. Herndon, Amany Hassan, Kennan Oyen, Karen C. Poh, Glen A. Scoles and Lindsay M. Fry
Pathogens 2023, 12(4), 559; https://doi.org/10.3390/pathogens12040559 - 5 Apr 2023
Cited by 5 | Viewed by 2654
Abstract
Theileria orientalis Ikeda has caused an epidemic of bovine anemia and abortion across several U.S. states. This apicomplexan hemoparasite is transmitted by Haemaphysalis longicornis ticks; however, it is unknown if other North American ticks are competent vectors. Since the disease movement is largely [...] Read more.
Theileria orientalis Ikeda has caused an epidemic of bovine anemia and abortion across several U.S. states. This apicomplexan hemoparasite is transmitted by Haemaphysalis longicornis ticks; however, it is unknown if other North American ticks are competent vectors. Since the disease movement is largely determined by the host tick range(s), the prediction of the T. orientalis spread among U.S. cattle populations requires determination of additional competent tick vectors. Although Rhipicephalus microplus has mostly been eradicated from the U.S., outbreaks in populations occur frequently, and the U.S. remains at risk for reintroduction. Since R. microplus is a vector of Theileria equi and T. orientalis DNA has been detected in R. microplus, the goal of this study was to determine whether R. microplus is a competent vector of T. orientalis. Larval R. microplus were applied to a splenectomized, T. orientalis Ikeda-infected calf for parasite acquisition, removed as molted adults, and applied to two T. orientalis naïve, splenectomized calves for transmission. After 60 days, the naïve calves remained negative for T. orientalis by PCR and cytology. Additionally, T. orientalis was not detected in the salivary glands or larval progeny of acquisition-fed adults. These data suggest that R. microplus is not a competent vector of the U.S. T. orientalis Ikeda isolate. Full article
(This article belongs to the Special Issue Ticks & Piroplasms: Updates and Emerging Challenges)
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9 pages, 1556 KiB  
Article
Effective Methods of Estimation of Pathogen Prevalence in Pooled Ticks
by Gerardo Fracasso, Marika Grillini, Laura Grassi, Francesco Gradoni, Graziana da Rold and Michela Bertola
Pathogens 2023, 12(4), 557; https://doi.org/10.3390/pathogens12040557 - 5 Apr 2023
Cited by 7 | Viewed by 2421
Abstract
Since tick-borne diseases (TBDs) incidence, both in human and animal populations, is increasing worldwide, there is the need to assess the presence, distribution and prevalence of tick-borne pathogens. Reliable estimates on tick-borne pathogens (TBPs) prevalence represent the public health foundation to create risk [...] Read more.
Since tick-borne diseases (TBDs) incidence, both in human and animal populations, is increasing worldwide, there is the need to assess the presence, distribution and prevalence of tick-borne pathogens. Reliable estimates on tick-borne pathogens (TBPs) prevalence represent the public health foundation to create risk maps and take effective prevention and control actions against TBDs. Tick surveillance consists of collecting and testing (usually in pools) thousands of specimens. Construction and analysis of tick pools represent a challenge due to the complexity of tick-borne pathogens and tick-borne diseases ecology. The aim of this study is to provide a practical guideline on appropriate pooling strategies and statistical analysis of infection prevalence through: (i) reporting the different pooling strategies and statistical methodologies commonly used to calculate pathogen prevalence in tick populations and (ii) practical comparison between statistical methods utilising a real dataset of infection prevalence in ticks collected in Northern Italy. Reporting detailed information on tick pool composition and size is as important as the correct TBPs prevalence estimation. Among the prevalence indexes, we suggest using maximum-likelihood estimates of pooled prevalence instead of minimum infection rate or pool positivity rate given the merits of the method and availability of software. Full article
(This article belongs to the Section Ticks)
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14 pages, 1152 KiB  
Review
Human Borrelia miyamotoi Infection in North America
by Jed Burde, Evan M. Bloch, Jill R. Kelly and Peter J. Krause
Pathogens 2023, 12(4), 553; https://doi.org/10.3390/pathogens12040553 - 3 Apr 2023
Cited by 6 | Viewed by 3201
Abstract
Borrelia miyamotoi is an emerging pathogen that causes a febrile illness and is transmitted by the same hard-bodied (ixodid) ticks that transmit several other pathogens, including Borrelia species that cause Lyme disease. B. miyamotoi was discovered in 1994 in Ixodes persulcatus ticks in [...] Read more.
Borrelia miyamotoi is an emerging pathogen that causes a febrile illness and is transmitted by the same hard-bodied (ixodid) ticks that transmit several other pathogens, including Borrelia species that cause Lyme disease. B. miyamotoi was discovered in 1994 in Ixodes persulcatus ticks in Japan. It was first reported in humans in 2011 in Russia. It has subsequently been reported in North America, Europe, and Asia. B. miyamotoi infection is widespread in Ixodes ticks in the northeastern, northern Midwestern, and far western United States and in Canada. In endemic areas, human B. miyamotoi seroprevalence averages from 1 to 3% of the population, compared with 15 to 20% for B. burgdorferi. The most common clinical manifestations of B. miyamotoi infection are fever, fatigue, headache, chills, myalgia, arthralgia, and nausea. Complications include relapsing fever and rarely, meningoencephalitis. Because clinical manifestations are nonspecific, diagnosis requires laboratory confirmation by PCR or blood smear examination. Antibiotics are effective in clearing infection and are the same as those used for Lyme disease, including doxycycline, tetracycline, erythromycin, penicillin, and ceftriaxone. Preventive measures include avoiding areas where B. miyamotoi-infected ticks are found, landscape management, and personal protective strategies such as protective clothing, use of acaricides, and tick checks with rapid removal of embedded ticks. Full article
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13 pages, 3174 KiB  
Article
Oral Supplementation with AHCC®, a Standardized Extract of Cultured Lentinula edodes Mycelia, Enhances Host Resistance against SARS-CoV-2 Infection
by Ankita Singh, Awadalkareem Adam, Leslie Rodriguez, Bi-Hung Peng, Binbin Wang, Xuping Xie, Pei-Yong Shi, Kohei Homma and Tian Wang
Pathogens 2023, 12(4), 554; https://doi.org/10.3390/pathogens12040554 - 3 Apr 2023
Cited by 1 | Viewed by 4548
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted global public health safety and the economy. Multiple antiviral drugs have been developed, and some have received regulatory approval and/or authorization. The use of nutraceuticals can be beneficial for preventing and treating COVID-19 complications. [...] Read more.
The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted global public health safety and the economy. Multiple antiviral drugs have been developed, and some have received regulatory approval and/or authorization. The use of nutraceuticals can be beneficial for preventing and treating COVID-19 complications. AHCC is a standardized, cultured extract of an edible mushroom Lentinula edodes of the Basidiomycete family of fungi that is enriched in acylated α-1,4-glucans. Here, we evaluated the effects of the oral administration of AHCC on the host response to SARS-CoV-2 infection in two murine models, K18-hACE2 transgenic mice and immunocompetent BALB/c mice. Oral administration of AHCC every other day for one week before and one day post SARS-CoV-2 infection in both strains of mice decreased the viral load and attenuated inflammation in the lungs. AHCC treatment also significantly reduced SARS-CoV-2-induced lethality in the K18-hACE2 mice. AHCC administration enhanced the expansion of γδ T cells in the spleen and lungs before and after viral infection and promoted T helper 1-prone mucosal and systemic T cell responses in both models. In AHCC-fed BALB/c mice, SARS-CoV-2 specific IgG responses were also enhanced. In summary, AHCC supplementation enhances host resistance against mild and severe COVID-19 infection primarily via the promotion of innate and adaptive T cell immune responses in mice. Full article
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11 pages, 10943 KiB  
Article
Novel Experimental Mouse Model to Study Malaria-Associated Acute Kidney Injury
by Johanna Bensalel, Alexandra Roberts, Kiara Hernandez, Angelica Pina, Winifred Prempeh, Blessing V. Babalola, Pablo Cannata, Alberto Lazaro and Julio Gallego-Delgado
Pathogens 2023, 12(4), 545; https://doi.org/10.3390/pathogens12040545 - 1 Apr 2023
Cited by 2 | Viewed by 2602
Abstract
The impact of malaria-associated acute kidney injury (MAKI), one of the strongest predictors of death in children with severe malaria (SM), has been largely underestimated and research in this area has been neglected. Consequently, a standard experimental mouse model to research this pathology [...] Read more.
The impact of malaria-associated acute kidney injury (MAKI), one of the strongest predictors of death in children with severe malaria (SM), has been largely underestimated and research in this area has been neglected. Consequently, a standard experimental mouse model to research this pathology is still lacking. The purpose of this study was to develop an in vivo model that resembles the pathology in MAKI patients. In this study, unilateral nephrectomies were performed on wild-type mice prior to infection with Plasmodium berghei NK65. The removal of one kidney has shown to be an effective approach to replicating the most common findings in humans with MAKI. Infection of nephrectomized mice, compared to their non-nephrectomized counterparts, resulted in the development of kidney injury, evident by histopathological analysis and elevated levels of acute kidney injury (AKI) biomarkers, including urinary neutrophil gelatinase-associated lipocalin, serum Cystatin C, and blood urea nitrogen. Establishment of this in vivo model of MAKI is critical to the scientific community, as it can be used to elucidate the molecular pathways implicated in MAKI, delineate the development of the disease, identify biomarkers for early diagnosis and prognosis, and test potential adjunctive therapies. Full article
(This article belongs to the Special Issue Pathology of Severe Malaria)
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12 pages, 2424 KiB  
Article
Role of Bacterial Surface Components in the Pathogenicity of Proteus mirabilis in a Murine Model of Catheter-Associated Urinary Tract Infection
by Roman Herout, Sara Khoddami, Igor Moskalev, Alina Reicherz, Ben H. Chew, Chelsie E. Armbruster and Dirk Lange
Pathogens 2023, 12(4), 509; https://doi.org/10.3390/pathogens12040509 - 24 Mar 2023
Cited by 3 | Viewed by 2386
Abstract
Proteus mirabilis (PM) is a Gram-negative, rod-shaped bacterium that causes catheter-associated urinary tract infections (CAUTIs). The specific roles of bacterial surface components (BSCs) in PM pathogenicity and CAUTIs remain unknown. To address this knowledge gap, we utilized relevant in vitro adhesion/invasion [...] Read more.
Proteus mirabilis (PM) is a Gram-negative, rod-shaped bacterium that causes catheter-associated urinary tract infections (CAUTIs). The specific roles of bacterial surface components (BSCs) in PM pathogenicity and CAUTIs remain unknown. To address this knowledge gap, we utilized relevant in vitro adhesion/invasion models and a well-established murine model of CAUTI to assess the ability of wildtype (WT) and seven mutant strains (MSs) of PM with deficiencies in various genes encoding BSCs to undergo the infectious process (including adhesion to catheters) in both model systems. Overall, MSs adhesion to catheters and the different cell types tested was significantly reduced compared to WT, while no invasion of cells was evident at 24 h. In vivo, WT showed a greater number of planktonic (urine) bacteria, bacteria adherent to catheters, and bacteria adherent to/invading bladder tissue when compared to the MSs. Bacterial counts in urine for PMI3191 and waaE mutants were lower than that for WT and other MSs. The complementation of mutated BSC genes resulting in the biggest defects restored the invasion phenotype both in vitro and in vivo. BSCs play a critical role at various steps in the pathogenicity of PM including adhesion to indwelling medical devices and adhesion/invasion of urinary tissue in vivo. Full article
(This article belongs to the Special Issue Molecular and Cellular Aspects of Urinary Tract Infection)
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15 pages, 1078 KiB  
Article
Hepatitis E Virus in Finland: Epidemiology and Risk in Blood Donors and in the General Population
by Jaana Mättö, Niina Putkuri, Ruska Rimhanen-Finne, Päivi Laurila, Jonna Clancy, Jarkko Ihalainen and Susanne Ekblom-Kullberg
Pathogens 2023, 12(3), 484; https://doi.org/10.3390/pathogens12030484 - 18 Mar 2023
Cited by 5 | Viewed by 2385
Abstract
Autochthonous hepatitis E (HEV) cases have been increasingly recognized and reported in Europe, caused predominantly by the zoonotic HEV genotype 3. The clinical picture is highly variable, from asymptomatic to acute severe or prolonged hepatitis in immunocompromised patients. The main route of transmission [...] Read more.
Autochthonous hepatitis E (HEV) cases have been increasingly recognized and reported in Europe, caused predominantly by the zoonotic HEV genotype 3. The clinical picture is highly variable, from asymptomatic to acute severe or prolonged hepatitis in immunocompromised patients. The main route of transmission to humans in Europe is the ingestion of undercooked pork meat. Transfusion-transmitted HEV infections have also been reported. The aim of the study was to determine the HEV epidemiology and risk in the Finnish blood donor population. A total of 23,137 samples from Finnish blood donors were screened for HEV RNA from individual samples and 1012 samples for HEV antibodies. Additionally, laboratory-confirmed hepatitis E cases in 2016–2022 were extracted from national surveillance data. The HEV RNA prevalence data was used to estimate the risk of transfusion transmission of HEV in the Finnish blood transfusion setting. Four HEV RNA-positive were found, resulting in 1:5784 (0.02%) RNA prevalence. All HEV RNA-positive samples were IgM-negative, and genotyped samples represented genotype HEV 3c. HEV IgG seroprevalence was 7.4%. From the HEV RNA rate found in this study and data on blood component usage in Finland in 2020, the risk estimate for a severe transfusion-transmitted HEV infection is 1:1,377,000 components or one in every 6–7 years. In conclusion, the results indicate that the risk of transfusion-transmitted HEV (HEV TTI) in Finland is low. However, continuous follow-up of the HEV epidemiology in relation to the transfusion risk landscape in Finland is necessary, as well as promoting awareness in the medical community of the small risk for HEV TTI, especially for immunocompromised patients. Full article
(This article belongs to the Special Issue Transfusion-Transmissible Infections and Epidemiological Surveillance)
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44 pages, 2206 KiB  
Review
Of Mycelium and Men: Inherent Human Susceptibility to Fungal Diseases
by Donald C. Vinh
Pathogens 2023, 12(3), 456; https://doi.org/10.3390/pathogens12030456 - 14 Mar 2023
Cited by 4 | Viewed by 5370
Abstract
In medical mycology, the main context of disease is iatrogenic-based disease. However, historically, and occasionally, even today, fungal diseases affect humans with no obvious risk factors, sometimes in a spectacular fashion. The field of “inborn errors of immunity” (IEI) has deduced at least [...] Read more.
In medical mycology, the main context of disease is iatrogenic-based disease. However, historically, and occasionally, even today, fungal diseases affect humans with no obvious risk factors, sometimes in a spectacular fashion. The field of “inborn errors of immunity” (IEI) has deduced at least some of these previously enigmatic cases; accordingly, the discovery of single-gene disorders with penetrant clinical effects and their immunologic dissection have provided a framework with which to understand some of the key pathways mediating human susceptibility to mycoses. By extension, they have also enabled the identification of naturally occurring auto-antibodies to cytokines that phenocopy such susceptibility. This review provides a comprehensive update of IEI and autoantibodies that inherently predispose humans to various fungal diseases. Full article
(This article belongs to the Special Issue Infection in Inborn Errors of Immunity)
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13 pages, 856 KiB  
Article
Pre-Vaccination Human Papillomavirus Genotypes and HPV16 Variants among Women Aged 25 Years or Less with Cervical Cancer
by Yasmin L. Jayasinghe, Sepehr N. Tabrizi, Matthew Stevens, Trishe Y-M. Leong, Jan Pyman, Sonia R. Grover, Suzanne M. Garland and the Early-Onset Cervical Cancer (EOCC) Study Group
Pathogens 2023, 12(3), 451; https://doi.org/10.3390/pathogens12030451 - 13 Mar 2023
Cited by 1 | Viewed by 1989
Abstract
Background: In 2007, Australia introduced a national human papillomavirus (HPV) vaccination program. In 2017, the onset of cervical screening changed from 18 to 25 years of age, utilising human papillomavirus (HPV) nucleic acid testing. The objective of the study is to describe the [...] Read more.
Background: In 2007, Australia introduced a national human papillomavirus (HPV) vaccination program. In 2017, the onset of cervical screening changed from 18 to 25 years of age, utilising human papillomavirus (HPV) nucleic acid testing. The objective of the study is to describe the HPV genotypes and HPV16 variants in biopsies from women ≤ 25 years of age with cervical carcinoma (CC) (cases), compared with those aged >25 years (controls), in a pre-vaccination cohort. Methods: HPV genotyping of archival paraffin blocks (n = 96) was performed using the INNO-LiPA HPV Genotyping assay. HPV16-positive samples were analysed for variants by type-specific PCR spanning L1, E2 and E6 regions. Results: HPV16 was the commonest genotype in cases (54.5%, 12/22) and controls (66.7%, 46/69) (p = 0.30), followed by HPV18 (36.3%, 8/22 vs. 17.3% 12/69, respectively) (p = 0.08). Furthermore, 90% (20/22) of cases and 84.1% (58/69) of controls were positive for HPV16 or 18 (p = 0.42); 100% (22/22) of cases and 95.7% (66/69) of controls had at least one genotype targeted by the nonavalent vaccine (p = 0.3). The majority of HPV16 variants (87.3%, 48/55) were of European lineage. The proportion of unique nucleotide substitutions was significantly higher in cases (83.3%, 10/12) compared with controls (34.1%, 15/44), (p < 0.003, χ2, OR 9.7, 95%CI 1.7–97.7). Conclusions: Virological factors may account for the differences in CCs observed in younger compared with older women. All CCs in young women in this study had preventable 9vHPV types, which is important messaging for health provider adherence to new cervical screening guidelines. Full article
(This article belongs to the Special Issue Latest Advances in Human Papillomavirus (HPV) Research)
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39 pages, 4465 KiB  
Review
Role of Innate Interferon Responses at the Ocular Surface in Herpes Simplex Virus-1-Induced Herpetic Stromal Keratitis
by Jiayi Ren, Ferrin Antony, Barry T. Rouse and Amol Suryawanshi
Pathogens 2023, 12(3), 437; https://doi.org/10.3390/pathogens12030437 - 10 Mar 2023
Cited by 11 | Viewed by 4766
Abstract
Herpes simplex virus type 1 (HSV-1) is a highly successful pathogen that primarily infects epithelial cells of the orofacial mucosa. After initial lytic replication, HSV-1 enters sensory neurons and undergoes lifelong latency in the trigeminal ganglion (TG). Reactivation from latency occurs throughout the [...] Read more.
Herpes simplex virus type 1 (HSV-1) is a highly successful pathogen that primarily infects epithelial cells of the orofacial mucosa. After initial lytic replication, HSV-1 enters sensory neurons and undergoes lifelong latency in the trigeminal ganglion (TG). Reactivation from latency occurs throughout the host’s life and is more common in people with a compromised immune system. HSV-1 causes various diseases depending on the site of lytic HSV-1 replication. These include herpes labialis, herpetic stromal keratitis (HSK), meningitis, and herpes simplex encephalitis (HSE). HSK is an immunopathological condition and is usually the consequence of HSV-1 reactivation, anterograde transport to the corneal surface, lytic replication in the epithelial cells, and activation of the host’s innate and adaptive immune responses in the cornea. HSV-1 is recognized by cell surface, endosomal, and cytoplasmic pattern recognition receptors (PRRs) and activates innate immune responses that include interferons (IFNs), chemokine and cytokine production, as well as the recruitment of inflammatory cells to the site of replication. In the cornea, HSV-1 replication promotes type I (IFN-α/β) and type III (IFN-λ) IFN production. This review summarizes our current understanding of HSV-1 recognition by PRRs and innate IFN-mediated antiviral immunity during HSV-1 infection of the cornea. We also discuss the immunopathogenesis of HSK, current HSK therapeutics and challenges, proposed experimental approaches, and benefits of promoting local IFN-λ responses. Full article
(This article belongs to the Special Issue Viruses and Ocular Infection)
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13 pages, 650 KiB  
Article
Field Resistance to Rose Rosette Disease as Determined by Multi-Year Evaluations in Tennessee and Delaware
by Mark T. Windham, Thomas Evans, Sara Collins, Juniper A. Lake, Jeekin Lau, Oscar Riera-Lizarazu and David H. Byrne
Pathogens 2023, 12(3), 439; https://doi.org/10.3390/pathogens12030439 - 10 Mar 2023
Cited by 1 | Viewed by 2824
Abstract
Rose rosette disease (RRD) caused by the rose rosette emaravirus (RRV) and transmitted by the eriophyid mite Phyllocoptes fructiphilus (Pf), both native to North America, has caused significant damage to roses over the last several decades. As cultural and chemical control of [...] Read more.
Rose rosette disease (RRD) caused by the rose rosette emaravirus (RRV) and transmitted by the eriophyid mite Phyllocoptes fructiphilus (Pf), both native to North America, has caused significant damage to roses over the last several decades. As cultural and chemical control of this disease is difficult and expensive, a field trial was established to systematically screen rose germplasm for potential sources of resistance. One hundred and eight rose accessions representing the diversity of rose germplasm were planted in Tennessee and Delaware, managed to encourage disease development, and evaluated for symptom development and viral presence for three years. All major commercial rose cultivars were susceptible to this viral disease to varying levels. The rose accessions with no or few symptoms were species accessions from the sections Cinnamomeae, Carolinae, Bracteatae, and Systylae or hybrids with these. Among these, some were asymptomatic; they displayed no symptoms but were infected by the virus. Their potential depends on their ability to serve as a source of viruses. The next step is to understand the mechanism of resistance and genetic control of the various sources of resistance identified. Full article
(This article belongs to the Special Issue Rose Rosette Disease)
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23 pages, 3703 KiB  
Article
Simulation of Foot-and-Mouth Disease Spread and Effects of Mitigation Strategies to Support Veterinary Contingency Planning in Denmark
by Beate Conrady, Sten Mortensen, Søren Saxmose Nielsen, Hans Houe, Francisco Fernando Calvo-Artavia, Johanne Ellis-Iversen and Anette Boklund
Pathogens 2023, 12(3), 435; https://doi.org/10.3390/pathogens12030435 - 9 Mar 2023
Cited by 4 | Viewed by 2579
Abstract
To forge a path towards livestock disease emergency preparedness in Denmark, 15 different strategies to mitigate foot-and-mouth disease (FMD) were examined by modelling epidemics initiated in cattle, pig or small ruminant herds across various production systems located in four different Danish regions (Scenario [...] Read more.
To forge a path towards livestock disease emergency preparedness in Denmark, 15 different strategies to mitigate foot-and-mouth disease (FMD) were examined by modelling epidemics initiated in cattle, pig or small ruminant herds across various production systems located in four different Danish regions (Scenario 1), or in one specific livestock production system within each of the three species geographically distributed throughout Denmark (Scenario 2). When additional mitigation strategies were implemented on top of basic control strategies in the European foot-and-mouth disease spread model (EuFMDiS), no significant benefits were predicted in terms of the number of infected farms, the epidemic control duration, and the total economic cost. Further, the model results indicated that the choice of index herd, the resources for outbreak control, and the detection time of FMD significantly influenced the course of an epidemic. The present study results emphasise the importance of basic mitigation strategies, including an effective back-and-forward traceability system, adequate resources for outbreak response, and a high level of awareness among farmers and veterinarians concerning the detection and reporting of FMD at an early stage of an outbreak for FMD control in Denmark. Full article
(This article belongs to the Special Issue Monitoring, Prevention and Control of Infectious Animal Diseases)
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20 pages, 5734 KiB  
Review
Occurrence, Distribution, and Management of Aphid-Transmitted Viruses in Cucurbits in Spain
by Celia De Moya-Ruiz, Pedro Gómez and Miguel Juárez
Pathogens 2023, 12(3), 422; https://doi.org/10.3390/pathogens12030422 - 7 Mar 2023
Cited by 6 | Viewed by 3705
Abstract
The effectiveness of pest and disease management in crops relies on knowledge about their presence and distribution in crop-producing areas. Aphids and whiteflies are among the main threats to vegetable crops since these hemipterans feed on plants, causing severe damage, and are also [...] Read more.
The effectiveness of pest and disease management in crops relies on knowledge about their presence and distribution in crop-producing areas. Aphids and whiteflies are among the main threats to vegetable crops since these hemipterans feed on plants, causing severe damage, and are also able to transmit a large number of devastating plant viral diseases. In particular, the widespread occurrence of aphid-transmitted viruses in cucurbit crops, along with the lack of effective control measures, makes surveillance programs and virus epidemiology necessary for providing sound advice and further integration into the management strategies that can ensure sustainable food production. This review describes the current presence and distribution of aphid-transmitted viruses in cucurbits in Spain, providing valuable epidemiological information, including symptom expressions of virus-infected plants for further surveillance and viral detection. We also provide an overview of the current measures for virus infection prevention and control strategies in cucurbits and indicate the need for further research and innovative strategies against aphid pests and their associated viral diseases. Full article
(This article belongs to the Special Issue Emerging and Re-emerging Plant Viruses in a Context of Global Change)
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12 pages, 684 KiB  
Review
Preventing Persistence of HPV Infection with Natural Molecules
by Antonio Simone Laganà, Vito Chiantera, Sandro Gerli, Sara Proietti, Elisa Lepore, Vittorio Unfer, Jose Carugno and Alessandro Favilli
Pathogens 2023, 12(3), 416; https://doi.org/10.3390/pathogens12030416 - 6 Mar 2023
Cited by 8 | Viewed by 8627
Abstract
Human papillomavirus (HPV) infection is one the most common sexually transmitted infections worldwide. In most cases, the infection is temporary and asymptomatic; however, when persistent, it may lead to lesions that can evolve into cancer in both women and men. Nowadays, prophylactic vaccination [...] Read more.
Human papillomavirus (HPV) infection is one the most common sexually transmitted infections worldwide. In most cases, the infection is temporary and asymptomatic; however, when persistent, it may lead to lesions that can evolve into cancer in both women and men. Nowadays, prophylactic vaccination is the primary preventive strategy for HPV infections, but vaccines do not cover all types of HPV strains. Scientific research has uncovered the beneficial role of some natural supplements in preventing persistent HPV infections or treating HPV-related lesions. We review the current insight into the roles of natural molecules in HPV infection with a special focus on epigallocatechin gallate (EGCG), folic acid, vitamin B12, and hyaluronic acid (HA). Specifically, EGCG from green tea extracts plays a critical role in suppressing HPV oncogenes and oncoproteins (E6/E7), which are responsible for HPV oncogenic activity and cancer development. Folic acid and vitamin B12 are essential vitamins for multiple functions in the body, and accumulating evidence suggests their importance in maintaining a high degree of methylation of the HPV genome, thus decreasing the likelihood of causing malignant lesions. HA, due to its re-epithelizing property, may prevent HPV virus entry in damaged mucosa and epithelia. Thereby, based on these premises, the combination of EGCG, folic acid, vitamin B12, and HA may be a very promising therapeutic approach to prevent HPV persistence. Full article
(This article belongs to the Special Issue Epidemiology of Human Papillomavirus Infection)
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13 pages, 792 KiB  
Review
Effective Treatments of UTI—Is Intravesical Therapy the Future?
by Chris J. Morris, Jennifer L. Rohn, Scott Glickman and Kylie J. Mansfield
Pathogens 2023, 12(3), 417; https://doi.org/10.3390/pathogens12030417 - 6 Mar 2023
Cited by 6 | Viewed by 3034
Abstract
Urinary tract infection (UTI) afflicts millions of patients globally each year. While the majority of UTIs are successfully treated with orally administered antibiotics, the impact of oral antibiotics on the host microbiota is under close research scrutiny and the potential for dysbiosis is [...] Read more.
Urinary tract infection (UTI) afflicts millions of patients globally each year. While the majority of UTIs are successfully treated with orally administered antibiotics, the impact of oral antibiotics on the host microbiota is under close research scrutiny and the potential for dysbiosis is a cause for concern. Optimal treatment of UTI relies upon the selection of an agent which displays appropriate pharmacokinetic-pharmacodynamic (PK-PD) properties that will deliver appropriately high concentrations in the urinary tract after oral administration. Alternatively, high local concentrations of antibiotic at the urothelial surface can be achieved by direct instillation into the urinary tract. For antibiotics with the appropriate physicochemical properties, this can be of critical importance in cases for which an intracellular urothelial bacterial reservoir is suspected. In this review, we summarise the underpinning biopharmaceutical barriers to effective treatment of UTI and provide an overview of the evidence for the deployment of the intravesical administration route for antibiotics. Full article
(This article belongs to the Special Issue Molecular and Cellular Aspects of Urinary Tract Infection)
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18 pages, 1547 KiB  
Article
Bacterial and Viral Pathogens with One Health Relevance in Invasive Raccoons (Procyon lotor, Linné 1758) in Southwest Germany
by Nico P. Reinhardt, Judith Köster, Astrid Thomas, Janosch Arnold, Robert Fux and Reinhard K. Straubinger
Pathogens 2023, 12(3), 389; https://doi.org/10.3390/pathogens12030389 - 1 Mar 2023
Cited by 4 | Viewed by 2647
Abstract
In Europe, raccoons are invasive neozoons with their largest population in Germany. Globally, this mesocarnivore acts as a wildlife reservoir for many (non-)zoonotic (re-)emerging pathogens, but very little epidemiological data is available for southwest Germany. This exploratory study aimed to screen free-ranging raccoons [...] Read more.
In Europe, raccoons are invasive neozoons with their largest population in Germany. Globally, this mesocarnivore acts as a wildlife reservoir for many (non-)zoonotic (re-)emerging pathogens, but very little epidemiological data is available for southwest Germany. This exploratory study aimed to screen free-ranging raccoons in Baden-Wuerttemberg (BW, Germany) for the occurrence of selected pathogens with One Health relevance. Organ tissue and blood samples collected from 102 animals, obtained by hunters in 2019 and 2020, were subsequently analysed for two bacterial and four viral pathogens using a qPCR approach. Single samples were positive for the carnivore protoparvovirus-1 (7.8%, n = 8), canine distemper virus (6.9%, n = 7), pathogenic Leptospira spp. (3.9%, n = 4) and Anaplasma phagocytophilum (15.7%, n = 16). West Nile virus and influenza A virus were not detected. Due to their invasive behaviour and synanthropic habit, raccoons may increase the risk of infections for wildlife, domestic animals, zoo animals and humans by acting as a link between them. Therefore, further studies should be initiated to evaluate these risks. Full article
(This article belongs to the Special Issue Surveillance of Zoonotic Pathogens Carried by Wildlife)
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15 pages, 5718 KiB  
Article
Design and Optimization of a Monkeypox virus Specific Serological Assay
by Taha Y. Taha, Michael B. Townsend, Jan Pohl, Kevin L. Karem, Inger K. Damon, Placide Mbala Kingebeni, Jean-Jacques Muyembe Tamfum, James W. Martin, Phillip R. Pittman, John W. Huggins, Panayampalli S. Satheshkumar, Dennis A. Bagarozzi, Jr., Mary G. Reynolds and Laura J. Hughes
Pathogens 2023, 12(3), 396; https://doi.org/10.3390/pathogens12030396 - 1 Mar 2023
Cited by 7 | Viewed by 3036
Abstract
Monkeypox virus (MPXV), a member of the Orthopoxvirus (OPXV) genus, is a zoonotic virus, endemic to central and western Africa that can cause smallpox-like symptoms in humans with fatal outcomes in up to 15% of patients. The incidence of MPXV infections in the [...] Read more.
Monkeypox virus (MPXV), a member of the Orthopoxvirus (OPXV) genus, is a zoonotic virus, endemic to central and western Africa that can cause smallpox-like symptoms in humans with fatal outcomes in up to 15% of patients. The incidence of MPXV infections in the Democratic Republic of the Congo, where the majority of cases have occurred historically, has been estimated to have increased as much as 20-fold since the end of smallpox vaccination in 1980. Considering the risk global travel carries for future disease outbreaks, accurate epidemiological surveillance of MPXV is warranted as demonstrated by the recent Mpox outbreak, where the majority of cases were occurring in non-endemic areas. Serological differentiation between childhood vaccination and recent infection with MPXV or other OPXVs is difficult due to the high level of conservation within OPXV proteins. Here, a peptide-based serological assay was developed to specifically detect exposure to MPXV. A comparative analysis of immunogenic proteins across human OPXVs identified a large subset of proteins that could potentially be specifically recognized in response to a MPXV infection. Peptides were chosen based upon MPXV sequence specificity and predicted immunogenicity. Peptides individually and combined were screened in an ELISA against serum from well-characterized Mpox outbreaks, vaccinee sera, and smallpox sera collected prior to eradication. One peptide combination was successful with ~86% sensitivity and ~90% specificity. The performance of the assay was assessed against the OPXV IgG ELISA in the context of a serosurvey by retrospectively screening a set of serum specimens from the region in Ghana believed to have harbored the MPXV-infected rodents involved in the 2003 United States outbreak. Full article
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13 pages, 1195 KiB  
Article
Screening for Influenza and Morbillivirus in Seals and Porpoises in the Baltic and North Sea
by Iben Stokholm, Christine Baechlein, Sara Persson, Anna Roos, Anders Galatius, Line Anker Kyhn, Signe Sveegaard, Charlotte Bie Thøstesen, Morten Tange Olsen, Paul Becher and Ursula Siebert
Pathogens 2023, 12(3), 357; https://doi.org/10.3390/pathogens12030357 - 21 Feb 2023
Cited by 2 | Viewed by 2661
Abstract
Historically, the seals and harbour porpoises of the Baltic Sea and North Sea have been subjected to hunting, chemical pollutants and repeated mass mortalities, leading to significant population fluctuations. Despite the conservation implications and the zoonotic potential associated with viral disease outbreaks in [...] Read more.
Historically, the seals and harbour porpoises of the Baltic Sea and North Sea have been subjected to hunting, chemical pollutants and repeated mass mortalities, leading to significant population fluctuations. Despite the conservation implications and the zoonotic potential associated with viral disease outbreaks in wildlife, limited information is available on the circulation of viral pathogens in Baltic Sea seals and harbour porpoises. Here, we investigated the presence of the influenza A virus (IAV), the phocine distemper virus (PDV) and the cetacean morbillivirus (CeMV) in tracheal swabs and lung tissue samples from 99 harbour seals, 126 grey seals, 73 ringed seals and 78 harbour porpoises collected in the Baltic Sea and North Sea between 2002–2019. Despite screening 376 marine mammals collected over nearly two decades, we only detected one case of PDV and two cases of IAV linked to the documented viral outbreaks in seals in 2002 and 2014, respectively. Although we find no evidence of PDV and IAV during intermediate years, reports of isolated cases of PDV in North Sea harbour seals and IAV (H5N8) in Baltic and North Sea grey seals suggest introductions of those pathogens within the sampling period. Thus, to aid future monitoring efforts we highlight the need for a standardized and continuous sample collection of swabs, tissue and blood samples across Baltic Sea countries. Full article
(This article belongs to the Special Issue Wildlife Hosts Pathogen Interaction)
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29 pages, 2488 KiB  
Review
Orthopoxvirus Zoonoses—Do We Still Remember and Are Ready to Fight?
by Małgorzata Gieryńska, Lidia Szulc-Dąbrowska, Justyna Struzik, Karolina Paulina Gregorczyk-Zboroch, Matylda Barbara Mielcarska, Felix Ngosa Toka, Ada Schollenberger and Zuzanna Biernacka
Pathogens 2023, 12(3), 363; https://doi.org/10.3390/pathogens12030363 - 21 Feb 2023
Cited by 8 | Viewed by 2658
Abstract
The eradication of smallpox was an enormous achievement due to the global vaccination program launched by World Health Organization. The cessation of the vaccination program led to steadily declining herd immunity against smallpox, causing a health emergency of global concern. The smallpox vaccines [...] Read more.
The eradication of smallpox was an enormous achievement due to the global vaccination program launched by World Health Organization. The cessation of the vaccination program led to steadily declining herd immunity against smallpox, causing a health emergency of global concern. The smallpox vaccines induced strong, humoral, and cell-mediated immune responses, protecting for decades after immunization, not only against smallpox but also against other zoonotic orthopoxviruses that now represent a significant threat to public health. Here we review the major aspects regarding orthopoxviruses’ zoonotic infections, factors responsible for viral transmissions, as well as the emerging problem of the increased number of monkeypox cases recently reported. The development of prophylactic measures against poxvirus infections, especially the current threat caused by the monkeypox virus, requires a profound understanding of poxvirus immunobiology. The utilization of animal and cell line models has provided good insight into host antiviral defenses as well as orthopoxvirus evasion mechanisms. To survive within a host, orthopoxviruses encode a large number of proteins that subvert inflammatory and immune pathways. The circumvention of viral evasion strategies and the enhancement of major host defenses are key in designing novel, safer vaccines, and should become the targets of antiviral therapies in treating poxvirus infections. Full article
(This article belongs to the Special Issue Immune Response of the Host and Vaccine Development)
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17 pages, 2454 KiB  
Article
Discovery and Development Strategies for SARS-CoV-2 NSP3 Macrodomain Inhibitors
by Marion Schuller, Tryfon Zarganes-Tzitzikas, James Bennett, Stephane De Cesco, Daren Fearon, Frank von Delft, Oleg Fedorov, Paul E. Brennan and Ivan Ahel
Pathogens 2023, 12(2), 324; https://doi.org/10.3390/pathogens12020324 - 15 Feb 2023
Cited by 7 | Viewed by 3304
Abstract
The worldwide public health and socioeconomic consequences caused by the COVID-19 pandemic highlight the importance of increasing preparedness for viral disease outbreaks by providing rapid disease prevention and treatment strategies. The NSP3 macrodomain of coronaviruses including SARS-CoV-2 is among the viral protein repertoire [...] Read more.
The worldwide public health and socioeconomic consequences caused by the COVID-19 pandemic highlight the importance of increasing preparedness for viral disease outbreaks by providing rapid disease prevention and treatment strategies. The NSP3 macrodomain of coronaviruses including SARS-CoV-2 is among the viral protein repertoire that was identified as a potential target for the development of antiviral agents, due to its critical role in viral replication and consequent pathogenicity in the host. By combining virtual and biophysical screening efforts, we discovered several experimental small molecules and FDA-approved drugs as inhibitors of the NSP3 macrodomain. Analogue characterisation of the hit matter and crystallographic studies confirming binding modes, including that of the antibiotic compound aztreonam, to the active site of the macrodomain provide valuable structure–activity relationship information that support current approaches and open up new avenues for NSP3 macrodomain inhibitor development. Full article
(This article belongs to the Special Issue ADP-Ribosylation in Pathogens)
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12 pages, 1364 KiB  
Review
The Evolution of the Safety of Plasma Products from Pathogen Transmission—A Continuing Narrative
by Albert Farrugia
Pathogens 2023, 12(2), 318; https://doi.org/10.3390/pathogens12020318 - 15 Feb 2023
Cited by 6 | Viewed by 3504
Abstract
Chronic recipients of plasma products are at risk of infection from blood-borne pathogens as a result of their inevitable exposure to agents which will contaminate a plasma manufacturing pool made up of thousands of individual donations. The generation of such a pool is [...] Read more.
Chronic recipients of plasma products are at risk of infection from blood-borne pathogens as a result of their inevitable exposure to agents which will contaminate a plasma manufacturing pool made up of thousands of individual donations. The generation of such a pool is an essential part of the large-scale manufacture of these products and is required for good manufacturing practice (GMP). Early observations of the transmission of hepatitis by pooled plasma and serum led to the incorporation of heat treatment of the albumin solution produced by industrial Cohn fractionation of plasma. This led to an absence of pathogen transmission by albumin over decades, during which hepatitis continued to be transmitted by other early plasma fractions, as well as through mainstream blood transfusions. This risk was decreased greatly over the 1960s as an understanding of the epidemiology and viral aetiology of transfusion-transmitted hepatitis led to the exclusion of high-risk groups from the donor population and the development of a blood screening test for hepatitis B. Despite these measures, the first plasma concentrates to treat haemophilia transmitted hepatitis B and other, poorly understood, forms of parenterally transmitted hepatitis. These risks were considered to be acceptable given the life-saving nature of the haemophilia treatment products. The emergence of the human immunodeficiency virus (HIV) as a transfusion-transmitted infection in the early 1980s shifted the focus of attention to this virus, which proved to be vulnerable to a number of inactivation methods introduced during manufacture. Further developments in the field obviated the risk of hepatitis C virus (HCV) which had also infected chronic recipients of plasma products, including haemophilia patients and immunodeficient patients receiving immunoglobulin. The convergence of appropriate donor selection driven by knowledge of viral epidemiology, the development of blood screening now based on molecular diagnostics, and the incorporation of viral inactivation techniques in the manufacturing process are now recognised as constituting a “safety tripod” of measures contributing to safety from pathogen transmission. Of these three components, viral inactivation during manufacture is the major contributor and has proven to be the bulwark securing the safety of plasma derivatives over the past thirty years. Concurrently, the safety of banked blood and components continues to depend on donor selection and screening, in the absence of universally adopted pathogen reduction technology. This has resulted in an inversion in the relative safety of the products of blood banking compared to plasma products. Overall, the experience gained in the past decades has resulted in an absence of pathogen transmission from the current generation of plasma derivatives, but maintaining vigilance, and the surveillance of the emergence of infectious agents, is vital to ensure the continued efficacy of the measures in place and the development of further interventions aimed at obviating safety threats. Full article
(This article belongs to the Special Issue Transfusion-Transmissible Infections and Epidemiological Surveillance)
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16 pages, 1115 KiB  
Review
HPV and Cervical Cancer: A Review of Epidemiology and Screening Uptake in the UK
by Sunyoung Choi, Ayden Ismail, George Pappas-Gogos and Stergios Boussios
Pathogens 2023, 12(2), 298; https://doi.org/10.3390/pathogens12020298 - 11 Feb 2023
Cited by 46 | Viewed by 11388
Abstract
Cervical cancer is the fourth most common malignancy in females worldwide, and a leading cause of death in the United Kingdom (UK). The human papillomavirus (HPV) is the strongest risk factor for developing cervical intraepithelial neoplasia and cancer. Across the UK, the national [...] Read more.
Cervical cancer is the fourth most common malignancy in females worldwide, and a leading cause of death in the United Kingdom (UK). The human papillomavirus (HPV) is the strongest risk factor for developing cervical intraepithelial neoplasia and cancer. Across the UK, the national HPV immunisation programme, introduced in 2008, has been successful in protecting against HPV-related infections. Furthermore, the National Health Service (NHS) implemented the cytology-based cervical cancer screening service to all females aged 25 to 64, which has observed a decline in cervical cancer incidence. In the UK, there has been an overall decline in age-appropriate coverage since April 2010. In 2019, the COVID-19 pandemic disrupted NHS cancer screening and immunisation programmes, leading to a 6.8% decreased uptake of cervical cancer screening from the previous year. Engagement with screening has also been associated with social deprivation. In England, incidence rates of cervical cancer were reported to be 65% higher in the most deprived areas compared to the least, with lifestyle factors such as cigarette consumption contributing to 21% of cervical cancer cases. In this article, we provide an update on the epidemiology of cervical cancer, and HPV pathogenesis and transmission, along with the current prevention programmes within the NHS. Full article
(This article belongs to the Special Issue Oncopathogens)
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17 pages, 587 KiB  
Review
Advances in Babesia Vaccine Development: An Overview
by Michał Jerzak, Albert Gandurski, Marta Tokaj, Weronika Stachera, Magdalena Szuba and Monika Dybicz
Pathogens 2023, 12(2), 300; https://doi.org/10.3390/pathogens12020300 - 11 Feb 2023
Cited by 9 | Viewed by 4939
Abstract
Babesiosis is a tick-borne zoonotic disease, which is caused by various species of intracellular Babesia parasite. It is a problem not only for the livestock industry but also for global health. Significant global economic losses, in particular in cattle production, have been observed. [...] Read more.
Babesiosis is a tick-borne zoonotic disease, which is caused by various species of intracellular Babesia parasite. It is a problem not only for the livestock industry but also for global health. Significant global economic losses, in particular in cattle production, have been observed. Since the current preventive measures against babesiosis are insufficient, there is increasing pressure to develop a vaccine. In this review, we survey the achievements and recent advances in the creation of antibabesiosis vaccine. The scope of this review includes the development of a vaccine against B. microti, B. bovis, B. bigemina, B. orientalis and B. divergens. Here, we present different strategies in their progress and evaluation. Scientists worldwide are still trying to find new targets for a vaccine that would not only reduce symptoms among animals but also prevent the further spread of the disease. Molecular candidates for the production of a vaccine against various Babesia spp. are presented. Our study also describes the current prospects of vaccine evolution for successful Babesia parasites elimination. Full article
(This article belongs to the Special Issue Immune Response of the Host and Vaccine Development)
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