Pathogens

19 pages, 2241 KiB

Open AccessEditor’s ChoiceArticle

Interactions of Mycoplasma hyopneumoniae and/or Mycoplasma hyorhinis with Streptococcus suis Serotype 2 Using In Vitro Co-Infection Models with Swine Cells

by Héloïse Pageaut, Sonia Lacouture, Mélanie Lehoux, Corinne Marois-Créhan, Mariela Segura and Marcelo Gottschalk

Pathogens 2023, 12(7), 866; https://doi.org/10.3390/pathogens12070866 - 22 Jun 2023

Cited by 1 | Viewed by 1634

Abstract

Bacterial and/or viral co-infections are very common in swine production and cause severe economic losses. Mycoplasma hyopneumoniae, Mycoplasma hyorhinis and Streptococcus suis are pathogenic bacteria that may be found simultaneously in the respiratory tracts of pigs. In the present study, the interactions [...] Read more.

Bacterial and/or viral co-infections are very common in swine production and cause severe economic losses. Mycoplasma hyopneumoniae, Mycoplasma hyorhinis and Streptococcus suis are pathogenic bacteria that may be found simultaneously in the respiratory tracts of pigs. In the present study, the interactions of S. suis with epithelial and phagocytic cells in the presence or absence of a pre-infection with M. hyopneumoniae and/or M. hyorhinis were studied. Results showed relatively limited interactions between these pathogens. A previous infection with one or both mycoplasmas did not influence the adhesion or invasion properties of S. suis in epithelial cells or its resistance to phagocytosis (including intracellular survival) by macrophages and dendritic cells. The most important effect observed during the co-infection was a clear increment in toxicity for the cells. An increase in the relative expression of the pro-inflammatory cytokines IL-6 and CXCL8 was also observed; however, this was the consequence of an additive effect due to the presence of different pathogens rather than a synergic effect. It may be hypothesized that if one or both mycoplasmas are present along with S. suis in the lower respiratory tract at the same time, then increased damage to epithelial cells and phagocytes, as well as an increased release of pro-inflammatory cytokines, may eventually enhance the invasive properties of S. suis. However, more studies should be carried out to confirm this hypothesis. Full article

(This article belongs to the Special Issue The Biology of Streptococcus and Streptococcal Infection)

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21 pages, 737 KiB

Open AccessEditor’s ChoiceArticle

Risk Factors for Hepatitis E Virus Infection and Eating Habits in Kidney Transplant Recipients

by Eva Wu, Nadine Koch, Friederike Bachmann, Marten Schulz, Evelyn Seelow, Ulrike Weber, Johannes Waiser, Fabian Halleck, Mirko Faber, Claus-Thomas Bock, Kai-Uwe Eckardt, Klemens Budde, Jörg Hofmann, Peter Nickel and Mira Choi

Pathogens 2023, 12(6), 850; https://doi.org/10.3390/pathogens12060850 - 20 Jun 2023

Viewed by 1411

Abstract

There is a significant risk for ongoing and treatment-resistant courses of hepatitis E virus (HEV) infection in patients after solid organ transplantation. The aim of this study was to identify risk factors for the development of hepatitis E, including the dietary habits of [...] Read more.

There is a significant risk for ongoing and treatment-resistant courses of hepatitis E virus (HEV) infection in patients after solid organ transplantation. The aim of this study was to identify risk factors for the development of hepatitis E, including the dietary habits of patients. We conducted a retrospective single-center study with 59 adult kidney and combined kidney transplant recipients who were diagnosed with HEV infection between 2013 and 2020. The outcomes of HEV infections were analyzed during a median follow-up of 4.3 years. Patients were compared with a control cohort of 251 transplant patients with elevated liver enzymes but without evidence of an HEV infection. Patients’ alimentary exposures during the time before disease onset or diagnosis were assessed. Previous intense immunosuppression, especially treatment with high-dose steroids and rituximab, was a significant risk factor to acquire hepatitis E after solid organ transplantation. Only 11 out of 59 (18.6%) patients reached remission without further ribavirin (RBV) treatment. A total of 48 patients were treated with RBV, of which 19 patients (39.6%) had either viral rebounds after the end of treatment or did not reach viral clearance at all. Higher age (>60 years) and a BMI ≤ 20 kg/m² were risk factors for RBV treatment failure. Deterioration in kidney function with a drop in eGFR (p = 0.046) and a rise in proteinuria was more common in patients with persistent hepatitis E viremia. HEV infection was associated with the consumption of undercooked pork or pork products prior to infection. Patients also reported processing raw meat with bare hands at home more frequently than the controls. Overall, we showed that the intensity of immunosuppression, higher age, a low BMI and the consumption of undercooked pork meat correlated with the development of hepatitis E. Full article

(This article belongs to the Special Issue Hepatitis E Virus (HEV) Infection among Humans and Animals: Epidemiology, Clinical Characteristics, Treatment and Prevention)

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21 pages, 1445 KiB

Open AccessEditor’s ChoiceReview

An Overview of Angiostrongylus cantonensis (Nematoda: Angiostrongylidae), an Emerging Cause of Human Angiostrongylosis on the Indian Subcontinent

by Divakaran Pandian, Tomáš Najer and David Modrý

Pathogens 2023, 12(6), 851; https://doi.org/10.3390/pathogens12060851 - 20 Jun 2023

Cited by 3 | Viewed by 3589

Abstract

Human angiostrongylosis is an emerging zoonosis caused by the larvae of three species of metastrongyloid nematodes of the genus Angiostrongylus, with Angiostrongylus cantonensis (Chen, 1935) being dominant across the world. Its obligatory heteroxenous life cycle includes rats as definitive hosts, mollusks as intermediate [...] Read more.

Human angiostrongylosis is an emerging zoonosis caused by the larvae of three species of metastrongyloid nematodes of the genus Angiostrongylus, with Angiostrongylus cantonensis (Chen, 1935) being dominant across the world. Its obligatory heteroxenous life cycle includes rats as definitive hosts, mollusks as intermediate hosts, and amphibians and reptiles as paratenic hosts. In humans, the infection manifests as Angiostrongylus eosinophilic meningitis (AEM) or ocular form. Since there is no comprehensive study on the disease in the Indian subcontinent, our study aims at the growing incidence of angiostrongylosis in humans, alongside its clinical course and possible causes. A systematic literature search revealed 28 reports of 45 human cases from 1966 to 2022; eosinophilic meningitis accounted for 33 cases (75.5%), 12 cases were reported as ocular, 1 case was combined, and 1 case was unspecified. The presumed source of infection was reported in 5 cases only. Importantly, 22 AEM patients reported a history of eating raw monitor lizard (Varanus spp.) tissues in the past. As apex predators, monitor lizards accumulate high numbers of L3 responsible for acute illness in humans. For ocular cases, the source was not identified. Most cases were diagnosed based on nematode findings and clinical pathology (primarily eosinophilia in the cerebrospinal fluid). Only two cases were confirmed to be A. cantonensis, one by immunoblot and the other by q-PCR. Cases of angiostrongylosis have been reported in Delhi, Karnataka, Kerala, Maharashtra, Madhya Pradesh, Puducherry, Telangana, and West Bengal. With a population of more than 1.4 billion, India is one of the least studied areas for A. cantonensis. It is likely that many cases remain undetected/unreported. Since most cases have been reported from the state of Kerala, further research may focus on this region. Gastropods, amphibians, and reptiles are commonly consumed in India; however, typical preparation methods involve cooking, which kills the nematode larvae. In addition to studying rodent and mollusk hosts, monitor lizards can be used as effective sentinels. Sequence data are urgently needed to answer the question of the identity of Angiostrongylus-like metastrongylid nematodes isolated from all types of hosts. DNA-based diagnostic methods such as q-PCR and LAMP should be included in clinical diagnosis of suspected cases and in studies of genetic diversity and species identity of nematodes tentatively identified as A. cantonensis. Full article

(This article belongs to the Special Issue Rat Lungworm Disease)

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17 pages, 2003 KiB

Open AccessEditor’s ChoiceArticle

Evaluation of the Effect of Plectranthus amboinicus L. Leaf Extracts on the Bacterial Antioxidant System and Cell Membrane Integrity of Pseudomonas aeruginosa PA01 and Staphylococcus aureus NCTC8325

by Sheeba Sawant, Timothy C. Baldwin, Oliwia Metryka and Ayesha Rahman

Pathogens 2023, 12(6), 853; https://doi.org/10.3390/pathogens12060853 - 20 Jun 2023

Viewed by 1746

Abstract

Plectranthus amboinicus (Indian borage) has been extensively studied for its medicinal properties, which can be exploited to develop new antimicrobial therapeutics. The current study investigated the effect of Plectranthus amboinicus leaf extracts on the catalase activity, reactive oxygen species, lipid peroxidation, cytoplasmic membrane [...] Read more.

Plectranthus amboinicus (Indian borage) has been extensively studied for its medicinal properties, which can be exploited to develop new antimicrobial therapeutics. The current study investigated the effect of Plectranthus amboinicus leaf extracts on the catalase activity, reactive oxygen species, lipid peroxidation, cytoplasmic membrane permeability, and efflux pump activity in S. aureus NCTC8325 and P. aeruginosa PA01. As the enzyme catalase protects bacteria against oxidative stress, disruption of its activity creates an imbalance in reactive oxygen species (ROS) levels, which subsequently oxidizes lipid chains, leading to lipid peroxidation. In addition, bacterial cell membranes are a potential target for new antibacterial agents, as efflux pump systems play a crucial role in antimicrobial resistance. Upon exposure of the microorganisms to Indian borage leaf extracts, the observed catalase activity decreased by 60% and 20% in P. aeruginosa and S. aureus, respectively. The generation of ROS can cause oxidation reactions to occur within the polyunsaturated fatty acids of the lipid membranes and induce lipid peroxidation. To investigate these phenomena, the increase in ROS activity in P. aeruginosa and S. aureus was studied using H₂DCFDA, which is oxidized to 2′,7′-dichlorofluorescein (DCF) by ROS. Furthermore, the concentration of lipid peroxidation product (malondialdehyde) was assessed using the Thiobarbituric acid assay and was shown to increase by 42.4% and 42.5% in P. aeruginosa and S. aureus, respectively. The effect of the extracts on the cell membrane permeability was monitored using diSC3-5 dye and it was observed that the cell membrane permeability of P. aeruginosa increased by 58% and of S. aureus by 83%. The effect on efflux pump activity was investigated using Rhodamine-6-uptake assay, which displayed a decrease in efflux activity of 25.5% in P. aeruginosa and 24.2% in S. aureus after treatment with the extracts. This combination of different methods to study various bacterial virulence factors provides a more robust, mechanistic understanding of the effect of P. amboinicus extracts on P. aeruginosa and S. aureus. This study thus represents the first report of the assessment of the effect of Indian borage leaf extracts on bacterial antioxidant systems and bacterial cell membranes, and can facilitate the future development of bacterial resistance modifying agents derived from P. amboinicus. Full article

(This article belongs to the Special Issue Advances in Treatment of Biofilm Infections)

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23 pages, 1287 KiB

Open AccessEditor’s ChoiceReview

Metallic Nanoparticles and Core-Shell Nanosystems in the Treatment, Diagnosis, and Prevention of Parasitic Diseases

by Grzegorz Król, Kamila Fortunka, Michał Majchrzak, Ewelina Piktel, Paulina Paprocka, Angelika Mańkowska, Agata Lesiak, Maciej Karasiński, Agnieszka Strzelecka, Bonita Durnaś and Robert Bucki

Pathogens 2023, 12(6), 838; https://doi.org/10.3390/pathogens12060838 - 17 Jun 2023

Cited by 5 | Viewed by 1888

Abstract

The usage of nanotechnology in the fight against parasitic diseases is in the early stages of development, but it brings hopes that this new field will provide a solution to target the early stages of parasitosis, compensate for the lack of vaccines for [...] Read more.

The usage of nanotechnology in the fight against parasitic diseases is in the early stages of development, but it brings hopes that this new field will provide a solution to target the early stages of parasitosis, compensate for the lack of vaccines for most parasitic diseases, and also provide new treatment options for diseases in which parasites show increased resistance to current drugs. The huge physicochemical diversity of nanomaterials developed so far, mainly for antibacterial and anti-cancer therapies, requires additional studies to determine their antiparasitic potential. When designing metallic nanoparticles (MeNPs) and specific nanosystems, such as complexes of MeNPs, with the shell of attached drugs, several physicochemical properties need to be considered. The most important are: size, shape, surface charge, type of surfactants that control their dispersion, and shell molecules that should assure specific molecular interaction with targeted molecules of parasites’ cells. Therefore, it can be expected that the development of antiparasitic drugs using strategies provided by nanotechnology and the use of nanomaterials for diagnostic purposes will soon provide new and effective methods of antiparasitic therapy and effective diagnostic tools that will improve the prevention and reduce the morbidity and mortality caused by these diseases. Full article

(This article belongs to the Section Parasitic Pathogens)

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11 pages, 330 KiB

Open AccessEditor’s ChoiceArticle

Small Ruminant Lentivirus Infection in Sheep and Goats in North Portugal: Seroprevalence and Risk Factors

by João Jacob-Ferreira, Ana Cláudia Coelho, Ana Grau Vila, Delia Lacasta and Hélder Quintas

Pathogens 2023, 12(6), 829; https://doi.org/10.3390/pathogens12060829 - 14 Jun 2023

Viewed by 1647

Abstract

Small ruminant lentiviruses (SRLVs) are transmitted among ovine and caprine species. This disease is a severe problem for small ruminant production, not only for animals’ well-being but also for flocks’ efficiency. The main aim of this research was to quantify the seroprevalence and [...] Read more.

Small ruminant lentiviruses (SRLVs) are transmitted among ovine and caprine species. This disease is a severe problem for small ruminant production, not only for animals’ well-being but also for flocks’ efficiency. The main aim of this research was to quantify the seroprevalence and associated risk factors for SRLV infection in the northern region of Portugal. Samples were collected from a total of 150 flocks, of which 129 (86.0%; 95% CI: 80.67%–91.33%) had at least one seropositive animal. Out of 2607 individual blood samples, 1074 (41.2%) were positive for SRLVs. Risk factors associated with SRLV infection were species (caprine), age (>2 years old), flock size (>100 animals), production system (intensive), food production system (milk), type of activity (professional), participation in livestock competitions (yes), replacement young ewe bought (yes), and natural feeding management (yes). This knowledge empowers the implementation of effective preventive measures. Overall, biosecurity measures should be promoted and implemented with the main aim of reducing viral transmission and reducing the prevalence of this disease. We recognise that government authorities should promote and audit voluntary control and eradication programs in small ruminant flocks in the region studied. Full article

(This article belongs to the Special Issue Women’s Special Issue Series: Pathogens)

19 pages, 1722 KiB

Open AccessEditor’s ChoiceReview

Xylem Embolism and Pathogens: Can the Vessel Anatomy of Woody Plants Contribute to X. fastidiosa Resistance?

by Giambattista Carluccio, Davide Greco, Erika Sabella, Marzia Vergine, Luigi De Bellis and Andrea Luvisi

Pathogens 2023, 12(6), 825; https://doi.org/10.3390/pathogens12060825 - 12 Jun 2023

Cited by 4 | Viewed by 2123

Abstract

The maintenance of an intact water column in the xylem lumen several meters above the ground is essential for woody plant viability. In fact, abiotic and biotic factors can lead to the formation of emboli in the xylem, interrupting sap flow and causing [...] Read more.

The maintenance of an intact water column in the xylem lumen several meters above the ground is essential for woody plant viability. In fact, abiotic and biotic factors can lead to the formation of emboli in the xylem, interrupting sap flow and causing consequences on the health status of the plant. Anyway, the tendency of plants to develop emboli depends on the intrinsic features of the xylem, while the cyto-histological structure of the xylem plays a role in resistance to vascular pathogens, as in the case of the pathogenic bacterium Xylella fastidiosa. Analysis of the scientific literature suggests that on grapevine and olive, some xylem features can determine plant tolerance to vascular pathogens. However, the same trend was not reported in citrus, indicating that X. fastidiosa interactions with host plants differ by species. Unfortunately, studies in this area are still limited, with few explaining inter-cultivar insights. Thus, in a global context seriously threatened by X. fastidiosa, a deeper understanding of the relationship between the physical and mechanical characteristics of the xylem and resistance to stresses can be useful for selecting cultivars that may be more resistant to environmental changes, such as drought and vascular pathogens, as a way to preserve agricultural productions and ecosystems. Full article

(This article belongs to the Special Issue Pathogens in 2023)

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15 pages, 1779 KiB

Open AccessFeature PaperEditor’s ChoiceReview

Recent Insights into the Role of B Cells in Chronic Hepatitis B and C Infections

by Zgjim Osmani and Andre Boonstra

Pathogens 2023, 12(6), 815; https://doi.org/10.3390/pathogens12060815 - 08 Jun 2023

Cited by 2 | Viewed by 3018

Abstract

Chronic viral hepatitis infections, caused by the hepatitis B or C virus, are a major global health problem causing an estimated one million deaths each year. Immunological studies have classically focused on T cells, while B cells have largely been neglected. Emerging evidence, [...] Read more.

Chronic viral hepatitis infections, caused by the hepatitis B or C virus, are a major global health problem causing an estimated one million deaths each year. Immunological studies have classically focused on T cells, while B cells have largely been neglected. Emerging evidence, however, highlights a role for B cells in the immunopathogenesis of chronic hepatitis B and C infections. B cell responses appear to be altered across different clinical phases of chronic HBV infection and across stages of disease in chronic HCV infection. These B cell responses show signs of a more activated state with a simultaneous enrichment of phenotypically exhausted atypical memory B cells. Despite the fact that studies show an activating B cell signature in chronic viral hepatitis infection, antibody responses to HBsAg remain impaired in chronic HBV infection, and glycoprotein E2-specific neutralizing antibody responses remain delayed in the acute phase of HCV infection. At the same time, studies have reported that a subset of HBV- and HCV-specific B cells exhibit an exhausted phenotype. This may, at least in part, explain why antibody responses in chronic HBV and HCV patients are suboptimal. Here, we summarize recent findings and discuss upcoming research questions while looking forward to how new single-cell technologies could provide novel insights into the role of B cells in chronic viral hepatitis infections. Full article

(This article belongs to the Special Issue Research on Hepatitis B Virus: Past, Present, and Future)

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12 pages, 907 KiB

Open AccessEditor’s ChoiceReview

Roles of FcRn in Antigen-Presenting Cells during Autoimmunity and a Clinical Evaluation of Efgartigimod as an FcRn Blocker

by Yihan Zhou and Shisong Jiang

Pathogens 2023, 12(6), 817; https://doi.org/10.3390/pathogens12060817 - 08 Jun 2023

Viewed by 2392

Abstract

The immune system is a complex network of multiple cells, tissues, and organs that protects the body against foreign pathogenic invaders. However, the immune system may mistakenly attack healthy cells and tissues due to the cross-reactivity of anti-pathogen immunity, leading to autoimmunity by [...] Read more.

The immune system is a complex network of multiple cells, tissues, and organs that protects the body against foreign pathogenic invaders. However, the immune system may mistakenly attack healthy cells and tissues due to the cross-reactivity of anti-pathogen immunity, leading to autoimmunity by autoreactive T cells and/or autoantibody-secreting B cells. Autoantibodies can accumulate, resulting in tissue or organ damage. The neonatal crystallizable fragment receptor (FcRn) is an important factor in immune regulation through controlling the trafficking and recycling of immunoglobulin G (IgG) molecules, the most abundant antibody in humoral immunity. In addition to its role in IgG trafficking and recycling, FcRn is also involved in antigen presentation, which is a crucial step in the activation of the adaptive immune response via directing the internalization and trafficking of antigen-bound IgG immune complexes into compartments of degradation and presentation in antigen-presenting cells. Efgartigimod, an FcRn inhibitor, has shown promise in reducing the levels of autoantibodies and alleviating the autoimmune severity of myasthenia gravis, primary immune thrombocytopenia, and pemphigus vulgaris/foliaceus. This article aims to provide an overview of the importance of FcRn in antigen-presenting cells and its potential as a therapeutic target in autoimmune diseases, using efgartigimod as an example. Full article

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

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11 pages, 2286 KiB

Open AccessEditor’s ChoiceCommunication

Activation of Inflammasome during Bluetongue Virus Infection

by Marie Pourcelot, Rayane Amaral da Silva Moraes, Sandrine Lacour, Aurore Fablet, Grégory Caignard and Damien Vitour

Pathogens 2023, 12(6), 801; https://doi.org/10.3390/pathogens12060801 - 04 Jun 2023

Cited by 1 | Viewed by 1249

Abstract

Bluetongue virus (BTV), a double-stranded RNA virus belonging to the Sedoreoviridae family, provokes an economically important disease in ruminants. In this study, we show that the production of activated caspase-1 and interleukin 1 beta (IL-1β) is induced in BTV-infected cells. This response seems [...] Read more.

Bluetongue virus (BTV), a double-stranded RNA virus belonging to the Sedoreoviridae family, provokes an economically important disease in ruminants. In this study, we show that the production of activated caspase-1 and interleukin 1 beta (IL-1β) is induced in BTV-infected cells. This response seems to require virus replication since a UV-inactivated virus is unable to activate this pathway. In NLRP3^-/- cells, BTV could not trigger further IL-1β synthesis, indicating that it occurs through NLRP3 inflammasome activation. Interestingly, we observed differential activation levels in bovine endothelial cells depending on the tissue origin. In particular, inflammasome activation was stronger in umbilical cord cells, suggesting that these cells are more prone to induce the inflammasome upon BTV infection. Finally, the strength of the inflammasome activation also depends on the BTV strain, which points to the importance of viral origin in inflammasome modulation. This work reports the crucial role of BTV in the activation of the NLRP3 inflammasome and further shows that this activation relies on BTV replication, strains, and cell types, thus providing new insights into BTV pathogenesis. Full article

(This article belongs to the Special Issue Pathogenesis of Viral Diseases)

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16 pages, 1013 KiB

Open AccessEditor’s ChoiceReview

Opisthorchis viverrini—Current Understanding of the Neglected Hepatobiliary Parasite

by Matthias Yi Quan Liau, En Qi Toh and Vishalkumar Girishchandra Shelat

Pathogens 2023, 12(6), 795; https://doi.org/10.3390/pathogens12060795 - 02 Jun 2023

Cited by 6 | Viewed by 2042

Abstract

Opisthorchiasis due to Opisthorchis viverrini infection continues to be a significant public healthcare concern in various subregions of Southeast Asia, particularly in Thailand, Laos, Cambodia, Myanmar, and Vietnam. The main mode of transmission is via consumption of raw or undercooked fish, which is [...] Read more.

Opisthorchiasis due to Opisthorchis viverrini infection continues to be a significant public healthcare concern in various subregions of Southeast Asia, particularly in Thailand, Laos, Cambodia, Myanmar, and Vietnam. The main mode of transmission is via consumption of raw or undercooked fish, which is deeply embedded in the culture and tradition of the people living near the Mekong River. After ingestion, the flukes migrate to the bile ducts, potentially causing many hepatobiliary complications, including cholangitis, cholecystitis, cholelithiasis, advanced periductal fibrosis and cholangiocarcinoma. Several mechanisms of opisthorchiasis-associated cholangiocarcinogenesis have been proposed and elucidated in the past decade, providing insight and potential drug targets to prevent the development of the sinister complication. The gold standard for diagnosing opisthorchiasis is still via stool microscopy, but the advent of novel serological, antigen, and molecular tests shows promise as more convenient, alternative diagnostic methods. The mainstay of treatment of opisthorchiasis is praziquantel, while treatment of opisthorchiasis-associated cholangiocarcinoma depends on its anatomic subtype and resectability. Thus far, the most successful fluke control programme is the Lawa model based in Thailand, which raised awareness, incorporated education, and frequent surveillance of intermediate hosts to reduce transmission of opisthorchiasis. Development of vaccines using tetraspanins shows promise and is currently ongoing. Full article

(This article belongs to the Special Issue Hepatobiliary and Pancreatic Infections)

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14 pages, 2438 KiB

Open AccessEditor’s ChoiceArticle

Molecular Investigations of Two First Brucella suis Biovar 2 Infections Cases in French Dogs

by Guillaume Girault, Vitomir Djokic, Fathia Petot-Bottin, Ludivine Perrot, Bourgoin Thibaut, Hoffmann Sébastien, Acacia Ferreira Vicente, Claire Ponsart and Luca Freddi

Pathogens 2023, 12(6), 792; https://doi.org/10.3390/pathogens12060792 - 01 Jun 2023

Cited by 2 | Viewed by 2176

Abstract

Despite Brucella suis biovar 2’s (BSB2) active circulation in wildlife, no canine infections have been reported. The present paper is the first to describe two cases of BSB2 infections in French dogs. The first case occurred in 2020 and concerned a 13-year-old male [...] Read more.

Despite Brucella suis biovar 2’s (BSB2) active circulation in wildlife, no canine infections have been reported. The present paper is the first to describe two cases of BSB2 infections in French dogs. The first case occurred in 2020 and concerned a 13-year-old male neutered Border Collie with clinical signs of prostatitis. The urine culture revealed the excretion of significant levels of Brucella in the sample. The second case concerned a German Shepherd with bilateral orchitis, in which it was possible to detect Brucella colonies following neutering. HRM-PCR and classical biotyping methods classified both isolated strains as BSB2, in contrast to expected B. canis, which is usually the etiological agent of canine brucellosis in Europe. The wgSNP and MLVA analyses highlighted the genetic proximity of two isolates to BSB2 strains originating from wildlife. No pig farms were present in the proximity of either dog’s residence, ruling out potential spill over from infected pigs. Nevertheless, the dogs used to take walks in the surrounding forests, where contact with wildlife (i.e., wild boars or hares, or their excrements) was possible. These cases highlight the importance of adopting a One Health approach to control the presence of zoonotic bacteria in wild animals and avoid spillovers into domestic animals and, potentially, humans. Full article

(This article belongs to the Special Issue Molecular Epidemiology of Zoonotic Bacterial Pathogens)

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19 pages, 1079 KiB

Open AccessFeature PaperEditor’s ChoiceReview

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 3 | Viewed by 3650

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

(This article belongs to the Special Issue Plasmodium vivax and G6PD Deficiency: From Development of Novel Diagnostic Tools to Implementation into Routine Care)

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12 pages, 1372 KiB

Open AccessEditor’s ChoiceArticle

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 2121

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

Open AccessEditor’s ChoiceArticle

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 4 | Viewed by 3005

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

Open AccessEditor’s ChoiceSystematic 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 12 | Viewed by 3035

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

(This article belongs to the Special Issue Acute Respiratory Infections: Diagnosis, Treatment, Complications and Prevention)

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22 pages, 2064 KiB

Open AccessEditor’s ChoiceReview

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 1 | Viewed by 2747

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

Open AccessEditor’s ChoiceCommunication

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 1598

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

(This article belongs to the Special Issue Topical Advisory Panel Members’ Collection Series: Diagnostics, Surveillance and Management of Infectious Diseases)

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36 pages, 3850 KiB

Open AccessEditor’s ChoiceReview

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 2 | Viewed by 2536

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

Open AccessEditor’s ChoicePerspective

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 4 | Viewed by 2454

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

(This article belongs to the Special Issue Pathogenesis, Epidemiology, Host Response and Control of Lyme Disease and Other Tick-Borne Diseases)

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0 pages, 417 KiB

Open AccessEditor’s ChoiceReview

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 2 | Viewed by 3247

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

Open AccessEditor’s ChoiceArticle

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 1 | Viewed by 1941

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

Open AccessEditor’s ChoiceArticle

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 1 | Viewed by 1955

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

Open AccessEditor’s ChoiceArticle

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

Viewed by 1966

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

Open AccessEditor’s ChoiceArticle

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 - 08 May 2023

Cited by 2 | Viewed by 1893

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

(This article belongs to the Special Issue Plasmodium vivax and G6PD Deficiency: From Development of Novel Diagnostic Tools to Implementation into Routine Care)

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11 pages, 1103 KiB

Open AccessEditor’s ChoiceReview

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 - 03 May 2023

Cited by 3 | Viewed by 1948

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

(This article belongs to the Special Issue Insect-Pathogen Dynamic Interplay and its Effects on Sensory-Perception)

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19 pages, 3217 KiB

Open AccessEditor’s ChoiceArticle

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 - 03 May 2023

Cited by 4 | Viewed by 1942

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

Open AccessEditor’s ChoiceArticle

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 1 | Viewed by 1648

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

Open AccessEditor’s ChoiceReview

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 6 | Viewed by 4284

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

(This article belongs to the Special Issue Plasmodium vivax and G6PD Deficiency: From Development of Novel Diagnostic Tools to Implementation into Routine Care)

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17 pages, 2005 KiB

Open AccessEditor’s ChoiceReview

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 33 | Viewed by 16418

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

Open AccessEditor’s ChoiceReview

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 1 | Viewed by 2035

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

(This article belongs to the Special Issue What Does Not Kill Them, Makes Them Stronger: Is the Inappropriate Use of Biocides a Driver of Antimicrobial Resistance?)

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23 pages, 831 KiB

Open AccessEditor’s ChoiceReview

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 4 | Viewed by 3228

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

Open AccessEditor’s ChoiceArticle

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 5 | Viewed by 2080

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

Open AccessEditor’s ChoiceReview

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 3 | Viewed by 3566

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

(This article belongs to the Special Issue Helicobacter pylori Resistance: New Natural Candidates for Therapeutical Approach)

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15 pages, 567 KiB

Open AccessEditor’s ChoiceArticle

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 3 | Viewed by 2117

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

Open AccessEditor’s ChoiceOpinion

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 - 09 Apr 2023

Cited by 2 | Viewed by 2406

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

(This article belongs to the Special Issue Pathogenesis, Epidemiology, Host Response and Control of Lyme Disease and Other Tick-Borne Diseases)

12 pages, 6616 KiB

Open AccessEditor’s ChoiceArticle

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 - 06 Apr 2023

Cited by 6 | Viewed by 2502

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

Open AccessEditor’s ChoiceSystematic 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 - 06 Apr 2023

Cited by 1 | Viewed by 1787

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

Open AccessEditor’s ChoiceArticle

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 - 06 Apr 2023

Cited by 4 | Viewed by 2699

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

Open AccessEditor’s ChoiceArticle

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 - 05 Apr 2023

Cited by 4 | Viewed by 2248

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

Open AccessEditor’s ChoiceArticle

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 - 05 Apr 2023

Cited by 1 | Viewed by 1941

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

Open AccessEditor’s ChoiceReview

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 - 03 Apr 2023

Cited by 5 | Viewed by 2627

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

(This article belongs to the Special Issue Pathogenesis, Epidemiology, Host Response and Control of Lyme Disease and Other Tick-Borne Diseases)

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13 pages, 3174 KiB

Open AccessEditor’s ChoiceArticle

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 - 03 Apr 2023

Cited by 1 | Viewed by 3712

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

(This article belongs to the Special Issue Emerging and Re-emerging Viral Infections: Towards Better Surveillance, Diagnosis, Treatment, and Control)

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11 pages, 10943 KiB

Open AccessEditor’s ChoiceArticle

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 - 01 Apr 2023

Cited by 1 | Viewed by 2135

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

Open AccessEditor’s ChoiceArticle

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 2 | Viewed by 1893

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

Open AccessEditor’s ChoiceArticle

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 3 | Viewed by 2005

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

Open AccessEditor’s ChoiceReview

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 3 | Viewed by 3988

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

Open AccessEditor’s ChoiceArticle

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 1692

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

Open AccessEditor’s ChoiceReview

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 6 | Viewed by 3858

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

Open AccessEditor’s ChoiceArticle

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 2414

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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