Pathogens

11 pages, 439 KB

Open AccessEditor’s ChoiceArticle

Neurocysticercosis Diagnosis in a Non-Endemic Country: France

by Ines Zemmour, Marie-Fleur Durieux, Etienne Herault, Célia Rouges, Barbara Šoba, Aurélien Mercier, Frédéric Ariey, Pierre-Marie Preux, Hélène Yera and on behalf of Collaborators Group

Pathogens 2023, 12(10), 1205; https://doi.org/10.3390/pathogens12101205 - 29 Sep 2023

Cited by 1 | Viewed by 2236

Abstract

Diagnosing neurocysticercosis (NCC) is difficult due to its variable clinical presentations and the different imaging techniques used to detect brain damage. This study aimed to evaluate the use of cerebrospinal fluid serology and PCR for diagnosing biological neurocysticercosis in a non-endemic country. We [...] Read more.

Diagnosing neurocysticercosis (NCC) is difficult due to its variable clinical presentations and the different imaging techniques used to detect brain damage. This study aimed to evaluate the use of cerebrospinal fluid serology and PCR for diagnosing biological neurocysticercosis in a non-endemic country. We tested samples from patients living in France with suspected NCC and confirmed that 45 of the patients presented with the disease. A total of 89% of patients had previously traveled to countries where the disease was endemic. The sensitivity of Western blots compared to ELISA was not significantly different (80% vs. 60%) (p > 0.05), and neither was the sensitivity of Western blots vs. PCR (78% vs. 56%) (p > 0.05). The PCR sensitivity was 78% and 47% in definitive NCC and in probable NCC. PCR tests using cerebrospinal fluid should be considered as a diagnostic criterion for identifying NCC. Full article

(This article belongs to the Special Issue Recent Advances in Taeniasis and Cysticercosis)

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34 pages, 2450 KB

Open AccessEditor’s ChoiceReview

The In Vitro Antimicrobial Susceptibility of Borrelia burgdorferi sensu lato: Shedding Light on the Known Unknowns

by Klaus-Peter Hunfeld, Peter Kraiczy, Douglas E. Norris and Benedikt Lohr

Pathogens 2023, 12(10), 1204; https://doi.org/10.3390/pathogens12101204 - 28 Sep 2023

Cited by 3 | Viewed by 4696

Abstract

Human Lyme borreliosis (LB) represents a multisystem disorder that can progress in stages. The causative agents are transmitted by hard ticks of the Ixodes ricinus complex that have been infected with the spirochete Borrelia burgdorferi sensu lato. Today, LB is considered the most [...] Read more.

Human Lyme borreliosis (LB) represents a multisystem disorder that can progress in stages. The causative agents are transmitted by hard ticks of the Ixodes ricinus complex that have been infected with the spirochete Borrelia burgdorferi sensu lato. Today, LB is considered the most important human tick-borne illness in the Northern Hemisphere. The causative agent was identified and successfully isolated in 1982 and, shortly thereafter, antibiotic treatment was found to be safe and efficacious. Since then, various in vitro studies have been conducted in order to improve our knowledge of the activity of antimicrobial agents against B. burgdorferi s. l. The full spectrum of in vitro antibiotic susceptibility has still not been defined for some of the more recently developed compounds. Moreover, our current understanding of the in vitro interactions between B. burgdorferi s. l. and antimicrobial agents, and their possible mechanisms of resistance remains very limited and is largely based on in vitro susceptibility experiments on only a few isolates of Borrelia. Even less is known about the possible mechanisms of the in vitro persistence of spirochetes exposed to antimicrobial agents in the presence of human and animal cell lines. Only a relatively small number of laboratory studies and cell culture experiments have been conducted. This review summarizes what is and what is not known about the in vitro susceptibility of B. burgdorferi s. l. It aims to shed light on the known unknowns that continue to fuel current debates on possible treatment resistance and mechanisms of persistence of Lyme disease spirochetes in the presence of antimicrobial agents. 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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14 pages, 995 KB

Open AccessEditor’s ChoiceReview

Epidemiology and Transmission of Theileria orientalis in Australasia

by Biniam T. Lakew, Steve Eastwood and Stephen W. Walkden-Brown

Pathogens 2023, 12(10), 1187; https://doi.org/10.3390/pathogens12101187 - 22 Sep 2023

Cited by 18 | Viewed by 4237

Abstract

Oriental theileriosis, a disease primarily impacting cattle is caused by an apicomplexan hemoprotozoan parasite, Theileria orientalis. It has now become established in the Australasia region. The organism was long considered a benign cause of persistent infections; however, an increase in clinical outbreaks [...] Read more.

Oriental theileriosis, a disease primarily impacting cattle is caused by an apicomplexan hemoprotozoan parasite, Theileria orientalis. It has now become established in the Australasia region. The organism was long considered a benign cause of persistent infections; however, an increase in clinical outbreaks since 2006 in the eastern Australian states and New Zealand was associated with the identification of the pathogenic Ikeda (Type 2) and Chitose (Type 1) genotypes. Unlike the pathogenic T. parva and T. annulate, which target leucocytes, clinical manifestation with T. orientalis is due to its effects on erythrocytes, with the infection sometimes designated as Theileria associated bovine anemia (TABA). In Australia and New Zealand, the tick Haemaphysalis longicornis is the principal vector, though other Haemaphysalis species are also likely vectors. The endemic status of infection with pathogenic genotypes in areas with low or absent tick populations is an apparent paradox that may be attributable to alternative modes of transmission, such as mechanical transmission by hematophagous insects (lice, mosquitoes, and biting flies), vertical transmission, and transmission via iatrogenic means. This review addresses the evidence for the different modes of transmission of T. orientalis with particular focus on the reported and potential vectors in Australasia. Full article

(This article belongs to the Special Issue Bovine Theileriosis Caused by the Theileria orientalis Group)

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20 pages, 2371 KB

Open AccessEditor’s ChoiceReview

Rift Valley Fever Virus—Infection, Pathogenesis and Host Immune Responses

by Niranjana Nair, Albert D. M. E. Osterhaus, Guus F. Rimmelzwaan and Chittappen Kandiyil Prajeeth

Pathogens 2023, 12(9), 1174; https://doi.org/10.3390/pathogens12091174 - 19 Sep 2023

Cited by 22 | Viewed by 6842

Abstract

Rift Valley Fever Virus is a mosquito-borne phlebovirus causing febrile or haemorrhagic illness in ruminants and humans. The virus can prevent the induction of the antiviral interferon response through its NSs proteins. Mutations in the NSs gene may allow the induction of innate [...] Read more.

Rift Valley Fever Virus is a mosquito-borne phlebovirus causing febrile or haemorrhagic illness in ruminants and humans. The virus can prevent the induction of the antiviral interferon response through its NSs proteins. Mutations in the NSs gene may allow the induction of innate proinflammatory immune responses and lead to attenuation of the virus. Upon infection, virus-specific antibodies and T cells are induced that may afford protection against subsequent infections. Thus, all arms of the adaptive immune system contribute to prevention of disease progression. These findings will aid the design of vaccines using the currently available platforms. Vaccine candidates have shown promise in safety and efficacy trials in susceptible animal species and these may contribute to the control of RVFV infections and prevention of disease progression in humans and ruminants. Full article

(This article belongs to the Special Issue Current Advances in Flavivirus and Other Arboviruses)

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14 pages, 2418 KB

Open AccessEditor’s ChoiceArticle

Interferon-λ Activates a Differential Response in Peripheral Neurons That Is Effective against Alpha Herpesvirus Infections

by Stephanie Salazar, Khanh T. Y. Luong, Taulima Nua and Orkide O. Koyuncu

Pathogens 2023, 12(9), 1142; https://doi.org/10.3390/pathogens12091142 - 7 Sep 2023

Cited by 4 | Viewed by 2643

Abstract

Alpha herpesviruses (α-HV) infect host mucosal epithelial cells prior to establishing a life-long latent infection in the peripheral nervous system. The initial spread of viral particles from mucosa to the nervous system and the role of intrinsic immune responses at this barrier is [...] Read more.

Alpha herpesviruses (α-HV) infect host mucosal epithelial cells prior to establishing a life-long latent infection in the peripheral nervous system. The initial spread of viral particles from mucosa to the nervous system and the role of intrinsic immune responses at this barrier is not well understood. Using primary neurons cultured in compartmentalized chambers, prior studies performed on Pseudorabies virus (PRV) have demonstrated that type I and type II interferons (IFNs) induce a local antiviral response in axons via distinct mechanisms leading to a reduction in viral particle transport to the neuronal nucleus. A new class of interferons known as type III IFNs has been shown to play an immediate role against viral infection in mucosal epithelial cells. However, the antiviral effects of type III IFNs within neurons during α-HV infection are largely unknown. In this study, we focused on elucidating the antiviral activity of type III IFN against PRV neuronal infection, and we compared the interferon-stimulated gene (ISGs) induction pattern in neurons to non-neuronal cells. We found that IFN pre-exposure of both primary neurons and fibroblast cells significantly reduces PRV virus yield, albeit by differential STAT activation and ISG induction patterns. Notably, we observed that type III IFNs trigger the expression of a subset of ISGs mainly through STAT1 activation to induce an antiviral state in primary peripheral neurons. Full article

(This article belongs to the Special Issue Host–Virus Interactions in the Nervous System)

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20 pages, 4370 KB

Open AccessEditor’s ChoiceArticle

Modulation of Macrophage Redox and Apoptotic Processes to Leishmania infantum during Coinfection with the Tick-Borne Bacteria Borrelia burgdorferi

by Danielle Pessôa-Pereira, Breanna M. Scorza, Karen I. Cyndari, Erin A. Beasley and Christine A. Petersen

Pathogens 2023, 12(9), 1128; https://doi.org/10.3390/pathogens12091128 - 4 Sep 2023

Cited by 3 | Viewed by 3777

Abstract

Canine leishmaniosis (CanL) is a zoonotic disease caused by protozoan Leishmania infantum. Dogs with CanL are often coinfected with tick-borne bacterial pathogens, including Borrelia burgdorferi in the United States. These coinfections have been causally associated with hastened disease progression and mortality. However, [...] Read more.

Canine leishmaniosis (CanL) is a zoonotic disease caused by protozoan Leishmania infantum. Dogs with CanL are often coinfected with tick-borne bacterial pathogens, including Borrelia burgdorferi in the United States. These coinfections have been causally associated with hastened disease progression and mortality. However, the specific cellular mechanisms of how coinfections affect microbicidal responses against L. infantum are unknown. We hypothesized that B. burgdorferi coinfection impacts host macrophage effector functions, prompting L. infantum intracellular survival. In vitro experiments demonstrated that exposure to B. burgdorferi spirochetes significantly increased L. infantum parasite burden and pro-inflammatory responses in DH82 canine macrophage cells. Induction of cell death and generation of mitochondrial ROS were significantly decreased in coinfected DH82 cells compared to uninfected and L. infantum-infected cells. Ex vivo stimulation of PBMCs from L. infantum-seronegative and -seropositive subclinical dogs with spirochetes and/or total Leishmania antigens promoted limited induction of IFNγ. Coexposure significantly induced expression of pro-inflammatory cytokines and chemokines associated with Th17 differentiation and neutrophilic and monocytic recruitment in PBMCs from L. infantum-seropositive dogs. Excessive pro-inflammatory responses have previously been shown to cause CanL pathology. This work supports effective tick prevention and risk management of coinfections as critical strategies to prevent and control L. infantum progression in dogs. Full article

(This article belongs to the Special Issue Host-Pathogen Interactions during Leishmania Infections—a Special Issue in Honor of Prof. Dr. John David)

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14 pages, 9317 KB

Open AccessEditor’s ChoiceArticle

Effects of Host Plants and Their Infection Status on Acquisition and Inoculation of A Plant Virus by Its Hemipteran Vector

by Saurabh Gautam, Kiran R. Gadhave, James W. Buck, Bhabesh Dutta, Timothy Coolong, Scott Adkins, Alvin M. Simmons and Rajagopalbabu Srinivasan

Pathogens 2023, 12(9), 1119; https://doi.org/10.3390/pathogens12091119 - 1 Sep 2023

Cited by 6 | Viewed by 2596

Abstract

Whitefly, Bemisia tabaci Gennadius (B cryptic species), transmits cucurbit leaf crumple virus (CuLCrV) in a persistent fashion. CuLCrV affects several crops such as squash and snap bean in the southeastern United States. CuLCrV is often found as a mixed infection with whitefly transmitted [...] Read more.

Whitefly, Bemisia tabaci Gennadius (B cryptic species), transmits cucurbit leaf crumple virus (CuLCrV) in a persistent fashion. CuLCrV affects several crops such as squash and snap bean in the southeastern United States. CuLCrV is often found as a mixed infection with whitefly transmitted criniviruses, such as cucurbit yellow stunting disorder virus (CYSDV) in hosts such as squash, or as a single infection in hosts such as snap bean. The implications of different host plants (inoculum sources) with varying infection status on CuLCrV transmission/epidemics is not clear. This study conducted a series of whitefly mediated CuLCrV transmission experiments. In the first experiment, three plants species: squash, snap bean, and tobacco were inoculated by whiteflies feeding on field-collected mixed-infected squash plants. In the second experiment, three plant species, namely squash, snap bean, and tobacco with varying infection status (squash infected with CuLCrV and CYSDV and snap bean and tobacco infected with CuLCrV), were used as inoculum sources. In the third experiment, squash plants with differential CuLCrV accumulation levels and infection status (either singly infected with CuLCrV or mixed infected with CuLCrV and CYSDV) were used as inoculum sources. Irrespective of plant species and its infection status, CuLCrV accumulation in whiteflies was dependent upon the CuLCrV accumulation in the inoculum source plants. Furthermore, differential CuLCrV accumulation in whiteflies resulted in differential transmission, CuLCrV accumulation, and disease phenotype in the recipient squash plants. Overall, results demonstrate that whitefly mediated CuLCrV transmission between host plants follows a virus density dependent phenomenon with implications for epidemics. Full article

(This article belongs to the Special Issue Emerging and Re-emerging Plant Viruses in a Context of Global Change)

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20 pages, 1408 KB

Open AccessEditor’s ChoiceReview

Reshaping Our Knowledge: Advancements in Understanding the Immune Response to Human Respiratory Syncytial Virus

by Federica Attaianese, Sara Guiducci, Sandra Trapani, Federica Barbati, Lorenzo Lodi, Giuseppe Indolfi, Chiara Azzari and Silvia Ricci

Pathogens 2023, 12(9), 1118; https://doi.org/10.3390/pathogens12091118 - 1 Sep 2023

Cited by 10 | Viewed by 3380

Abstract

Human respiratory syncytial virus (hRSV) is a significant cause of respiratory tract infections, particularly in young children and older adults. In this review, we aimed to comprehensively summarize what is known about the immune response to hRSV infection. We described the innate and [...] Read more.

Human respiratory syncytial virus (hRSV) is a significant cause of respiratory tract infections, particularly in young children and older adults. In this review, we aimed to comprehensively summarize what is known about the immune response to hRSV infection. We described the innate and adaptive immune components involved, including the recognition of RSV, the inflammatory response, the role of natural killer (NK) cells, antigen presentation, T cell response, and antibody production. Understanding the complex immune response to hRSV infection is crucial for developing effective interventions against this significant respiratory pathogen. Further investigations into the immune memory generated by hRSV infection and the development of strategies to enhance immune responses may hold promise for the prevention and management of hRSV-associated diseases. Full article

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

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22 pages, 3012 KB

Open AccessEditor’s ChoiceArticle

Mycobacterium tuberculosis Central Metabolism Is Key Regulator of Macrophage Pyroptosis and Host Immunity

by Michelle E. Maxson, Lahari Das, Michael F. Goldberg, Steven A. Porcelli, John Chan and William R. Jacobs, Jr.

Pathogens 2023, 12(9), 1109; https://doi.org/10.3390/pathogens12091109 - 30 Aug 2023

Cited by 3 | Viewed by 3713

Abstract

Metabolic dysregulation in Mycobacterium tuberculosis results in increased macrophage apoptosis or pyroptosis. However, mechanistic links between Mycobacterium virulence and bacterial metabolic plasticity remain ill defined. In this study, we screened random transposon insertions of M. bovis BCG to identify mutants that induce pyroptotic [...] Read more.

Metabolic dysregulation in Mycobacterium tuberculosis results in increased macrophage apoptosis or pyroptosis. However, mechanistic links between Mycobacterium virulence and bacterial metabolic plasticity remain ill defined. In this study, we screened random transposon insertions of M. bovis BCG to identify mutants that induce pyroptotic death of the infected macrophage. Analysis of the transposon insertion sites identified a panel of fdr (functioning death repressor) genes, which were shown in some cases to encode functions central to Mycobacterium metabolism. In-depth studies of one fdr gene, fdr8 (BCG3787/Rv3727), demonstrated its important role in the maintenance of M. tuberculosis and M. bovis BCG redox balance in reductive stress conditions in the host. Our studies expand the subset of known Mycobacterium genes linking bacterial metabolic plasticity to virulence and also reveal that the broad induction of pyroptosis by an intracellular bacterial pathogen is linked to enhanced cellular immunity in vivo. Full article

(This article belongs to the Special Issue Biology of Mycobacterial Pathogens)

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16 pages, 2793 KB

Open AccessEditor’s ChoiceArticle

Evaluation of a Tetracycline-Resistant E. coli Enumeration Method for Correctly Classifying E. coli in Environmental Waters in Kentucky, USA

by Callie Boggs, Kidus Shiferawe, Eckhardt Karsten, Jayden Hamlet, S. Travis Altheide and Jason W. Marion

Pathogens 2023, 12(9), 1090; https://doi.org/10.3390/pathogens12091090 - 28 Aug 2023

Cited by 5 | Viewed by 3482

Abstract

The global concern over antimicrobial resistance (AMR) and its impact on human health is evident, with approximately 4.95 million annual deaths attributed to antibiotic resistance. Regions with inadequate water, sanitation, and hygiene face challenges in responding to AMR threats. Enteric bacteria, particularly E. [...] Read more.

The global concern over antimicrobial resistance (AMR) and its impact on human health is evident, with approximately 4.95 million annual deaths attributed to antibiotic resistance. Regions with inadequate water, sanitation, and hygiene face challenges in responding to AMR threats. Enteric bacteria, particularly E. coli, are common agents linked to AMR-related deaths (23% of cases). Culture-based methods for detecting tetracycline-resistant E. coli may be of practical value for AMR monitoring in limited resource environments. This study evaluated the ColiGlow™ method with tetracycline for classifying tetracycline-resistant E. coli. A total of 61 surface water samples from Kentucky, USA (2020–2022), provided 61 presumed E. coli isolates, of which 28 isolates were obtained from tetracycline-treated media. Species identification and tetracycline resistance evaluation were performed. It was found that 82% of isolates were E. coli, and 18% were other species; 97% were identified as E. coli when using the API20E identification system. The MicroScan system yielded Enterobacter cloacae false positives in 20% of isolates. Adding tetracycline to ColiGlow increased the odds of isolating tetracycline-resistant E. coli 18-fold. Tetracycline-treated samples yielded 100% tetracycline-resistant E. coli when the total E. coli densities were within the enumeration range of the method. ColiGlow with tetracycline shows promise for monitoring tetracycline-resistant E. coli in natural waters and potentially aiding AMR surveillance in resource-limited settings among other environments. Full article

(This article belongs to the Special Issue Water-Borne Pathogens)

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17 pages, 9957 KB

Open AccessEditor’s ChoiceArticle

Evaluation of Wild Peanut Species and Their Allotetraploids for Resistance against Thrips and Thrips-Transmitted Tomato Spotted Wilt Orthotospovirus (TSWV)

by Yi-Ju Chen, Sudeep Pandey, Michael Catto, Soraya Leal-Bertioli, Mark R. Abney, Sudeep Bag, Mark Hopkins, Albert Culbreath and Rajagopalbabu Srinivasan

Pathogens 2023, 12(9), 1102; https://doi.org/10.3390/pathogens12091102 - 28 Aug 2023

Cited by 7 | Viewed by 2802

Abstract

Thrips-transmitted tomato spotted wilt orthotospovirus (TSWV) causes spotted wilt disease in peanut (Arachis hypogaea L.) and limits yield. Breeding programs have been developing TSWV-resistant cultivars, but availability of sources of resistance against TSWV in cultivated germplasm is extremely limited. Diploid wild Arachis [...] Read more.

Thrips-transmitted tomato spotted wilt orthotospovirus (TSWV) causes spotted wilt disease in peanut (Arachis hypogaea L.) and limits yield. Breeding programs have been developing TSWV-resistant cultivars, but availability of sources of resistance against TSWV in cultivated germplasm is extremely limited. Diploid wild Arachis species can serve as important sources of resistance, and despite ploidy barriers (cultivated peanut is tetraploid), their usage in breeding programs is now possible because of the knowledge and development of induced interspecific allotetraploid hybrids. This study screened 10 wild diploid Arachis and six induced allotetraploid genotypes via thrips-mediated TSWV transmission assays and thrips’ feeding assays in the greenhouse. Three parameters were evaluated: percent TSWV infection, virus accumulation, and temporal severity of thrips feeding injury. Results indicated that the diploid A. stenosperma accession V10309 and its derivative-induced allotetraploid ValSten1 had the lowest TSWV infection incidences among the evaluated genotypes. Allotetraploid BatDur1 had the lowest thrips-inflicted damage at each week post thrips release, while diploid A. batizocoi accession K9484 and A. duranensis accession V14167 had reduced feeding damage one week post thrips release, and diploids A. valida accession GK30011 and A. batizocoi had reduced feeding damage three weeks post thrips releasethan the others. Overall, plausible TSWV resistance in diploid species and their allotetraploid hybrids was characterized by reduced percent TSWV infection, virus accumulation, and feeding severity. Furthermore, a few diploids and tetraploid hybrids displayed antibiosis against thrips. These results document evidence for resistance against TSWV and thrips in wild diploid Arachis species and peanut-compatible-induced allotetraploids. Full article

(This article belongs to the Special Issue Emerging and Re-emerging Plant Viruses in a Context of Global Change)

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14 pages, 675 KB

Open AccessEditor’s ChoiceReview

Joining Forces against Antibiotic Resistance: The One Health Solution

by Eleonora Cella, Marta Giovanetti, Francesca Benedetti, Fabio Scarpa, Catherine Johnston, Alessandra Borsetti, Giancarlo Ceccarelli, Taj Azarian, Davide Zella and Massimo Ciccozzi

Pathogens 2023, 12(9), 1074; https://doi.org/10.3390/pathogens12091074 - 23 Aug 2023

Cited by 76 | Viewed by 11009

Abstract

Antibiotic resistance is a significant global health concern that affects both human and animal populations. The One Health approach acknowledges the interconnectedness of human health, animal health, and the environment. It emphasizes the importance of collaboration and coordination across these sectors to tackle [...] Read more.

Antibiotic resistance is a significant global health concern that affects both human and animal populations. The One Health approach acknowledges the interconnectedness of human health, animal health, and the environment. It emphasizes the importance of collaboration and coordination across these sectors to tackle complex health challenges such as antibiotic resistance. In the context of One Health, antibiotic resistance refers to the ability of bacteria to withstand the efficacy of antibiotics, rendering them less effective or completely ineffective in treating infections. The emergence and spread of antibiotic-resistant bacteria pose a threat to human and animal health, as well as to the effectiveness of medical treatments and veterinary interventions. In particular, One Health recognizes that antibiotic use in human medicine, animal agriculture, and the environment are interconnected factors contributing to the development and spread of antibiotic resistance. For example, the misuse and overuse of antibiotics in human healthcare, including inappropriate prescribing and patient non-compliance, can contribute to the selection and spread of resistant bacteria. Similarly, the use of antibiotics in livestock production for growth promotion and disease prevention can contribute to the development of antibiotic resistance in animals and subsequent transmission to humans through the food chain. Addressing antibiotic resistance requires a collaborative One Health approach that involves multiple participants, including healthcare professionals, veterinarians, researchers, and policymakers. Full article

(This article belongs to the Special Issue Reviews of Infectious Diseases)

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18 pages, 16402 KB

Open AccessEditor’s ChoiceArticle

Genomic and Phylogenetic Analysis of Bacillus cereus Biovar anthracis Isolated from Archival Bone Samples Reveals Earlier Natural History of the Pathogen

by Michael H. Norris, Diansy Zincke, David J. Daegling, John Krigbaum, W. Scott McGraw, Alexander Kirpich, Ted L. Hadfield and Jason K. Blackburn

Pathogens 2023, 12(8), 1065; https://doi.org/10.3390/pathogens12081065 - 20 Aug 2023

Cited by 3 | Viewed by 2928

Abstract

(1) Background: Bacillus cereus biovar anthracis (Bcbva) was the causative agent of an anthrax-like fatal disease among wild chimpanzees in 2001 in Côte d’Ivoire. Before this, there had not been any description of an anthrax-like disease caused by typically avirulent Bacillus cereus. Genetic [...] Read more.

(1) Background: Bacillus cereus biovar anthracis (Bcbva) was the causative agent of an anthrax-like fatal disease among wild chimpanzees in 2001 in Côte d’Ivoire. Before this, there had not been any description of an anthrax-like disease caused by typically avirulent Bacillus cereus. Genetic analysis found that B. cereus had acquired two anthrax-like plasmids, one a pXO1-like toxin producing plasmid and the other a pXO2-like plasmid encoding capsule. Bcbva caused animal fatalities in Cameroon, Democratic Republic of Congo, and the Central African Republic between 2004 and 2012. (2) Methods: The pathogen had acquired plasmids in the wild and that was discovered as the cause of widespread animal fatalities in the early 2000s. Primate bones had been shipped out of the endemic zone for anthropological studies prior to the realized danger of contamination with Bcbva. Spores were isolated from the bone fragments and positively identified as Bcbva. Strains were characterized by classical microbiological methods and qPCR. Four new Bcbva isolates were whole-genome sequenced. Chromosomal and plasmid phylogenomic analysis was performed to provide temporal and spatial context to these new strains and previously sequenced Bcbva. Tau and principal component analyses were utilized to identify genetic and spatial case patterns in the Taï National Park anthrax zone. (3) Results: Preliminary studies positively identified Bcbva presence in several archival bone fragments. The animals in question died between 1994 and 2010. Previously, the earliest archival strains of Bcbva were identified in 1996. Though the pathogen has a homogeneous genome, spatial analyses of a subset of mappable isolates from Taï National Park revealed strains found closer together were generally more similar, with strains from chimpanzees and duikers having the widest distribution. Ancestral strains were located mostly in the west of the park and had lower spatial clustering compared to more recent isolates, indicating a local increase in genetic diversity of Bcbva in the park over space and time. Global clustering analysis indicates patterns of genetic diversity and distance are shared between the ancestral and more recently isolated type strains. (4) Conclusions: Our strains have the potential to unveil historical genomic information not available elsewhere. This information sheds light on the evolution and emergence of a dangerous anthrax-causing pathogen. Full article

(This article belongs to the Special Issue Anthrax—a Threat beyond Bacillus anthracis)

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19 pages, 2303 KB

Open AccessEditor’s ChoiceReview

Malaria Genomics, Vaccine Development, and Microbiome

by Xinzhuan Su, Rachel V. Stadler, Fangzheng Xu and Jian Wu

Pathogens 2023, 12(8), 1061; https://doi.org/10.3390/pathogens12081061 - 18 Aug 2023

Cited by 4 | Viewed by 6907

Abstract

Recent advances in malaria genetics and genomics have transformed many aspects of malaria research in areas of molecular evolution, epidemiology, transmission, host–parasite interaction, drug resistance, pathogenicity, and vaccine development. Here, in addition to introducing some background information on malaria parasite biology, parasite genetics/genomics, [...] Read more.

Recent advances in malaria genetics and genomics have transformed many aspects of malaria research in areas of molecular evolution, epidemiology, transmission, host–parasite interaction, drug resistance, pathogenicity, and vaccine development. Here, in addition to introducing some background information on malaria parasite biology, parasite genetics/genomics, and genotyping methods, we discuss some applications of genetic and genomic approaches in vaccine development and in studying interactions with microbiota. Genetic and genomic data can be used to search for novel vaccine targets, design an effective vaccine strategy, identify protective antigens in a whole-organism vaccine, and evaluate the efficacy of a vaccine. Microbiota has been shown to influence disease outcomes and vaccine efficacy; studying the effects of microbiota in pathogenicity and immunity may provide information for disease control. Malaria genetics and genomics will continue to contribute greatly to many fields of malaria research. Full article

(This article belongs to the Special Issue Models in Parasite and Pathogen Evolution)

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14 pages, 1303 KB

Open AccessEditor’s ChoiceArticle

Biologically Relevant Murine Models of Chronic Pseudomonas aeruginosa Respiratory Infection

by Aoife M. Rodgers, Jaime Lindsay, Avril Monahan, Alice V. Dubois, Aduragbemi A. Faniyi, Barry J. Plant, Marcus A. Mall, Miquel B. Ekkelenkamp, Stuart Elborn and Rebecca J. Ingram

Pathogens 2023, 12(8), 1053; https://doi.org/10.3390/pathogens12081053 - 17 Aug 2023

Cited by 6 | Viewed by 3833

Abstract

Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen and the leading cause of infection in patients with cystic fibrosis (CF). The ability of P. aeruginosa to evade host responses and develop into chronic infection causes significant morbidity and mortality. Several mouse models have [...] Read more.

Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen and the leading cause of infection in patients with cystic fibrosis (CF). The ability of P. aeruginosa to evade host responses and develop into chronic infection causes significant morbidity and mortality. Several mouse models have been developed to study chronic respiratory infections induced by P. aeruginosa, with the bead agar model being the most widely used. However, this model has several limitations, including the requirement for surgical procedures and high mortality rates. Herein, we describe novel and adapted biologically relevant models of chronic lung infection caused by P. aeruginosa. Three methods are described: a clinical isolate infection model, utilising isolates obtained from patients with CF; an incomplete antibiotic clearance model, leading to bacterial bounce-back; and the establishment of chronic infection; and an adapted water bottle chronic infection model. These models circumvent the requirement for a surgical procedure and, importantly, can be induced with clinical isolates of P. aeruginosa and in wild-type mice. We also demonstrate successful induction of chronic infection in the transgenic βENaC murine model of CF. We envisage that the models described will facilitate the investigations of host and microbial factors, and the efficacy of novel antimicrobials, during chronic P. aeruginosa respiratory infections. Full article

(This article belongs to the Special Issue Animal Models of Infectious Disease-2nd Volume)

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13 pages, 710 KB

Open AccessEditor’s ChoiceArticle

Presence of Equine and Bovine Coronaviruses, Endoparasites, and Bacteria in Fecal Samples of Horses with Colic

by Moritz Stummer, Vicky Frisch, Frauke Glitz, Barbara Hinney, Joachim Spergser, Jürgen Krücken, Irina Diekmann, Katharina Dimmel, Christiane Riedel, Jessika-Maximiliane V. Cavalleri, Till Rümenapf, Anja Joachim, Manolis Lyrakis and Angelika Auer

Pathogens 2023, 12(8), 1043; https://doi.org/10.3390/pathogens12081043 - 15 Aug 2023

Cited by 5 | Viewed by 2785

Abstract

Acute abdominal pain (colic) is one of the major equine health threats worldwide and often necessitates intensive veterinary medical care and surgical intervention. Equine coronavirus (ECoV) infections can cause colic in horses but are rarely considered as a differential diagnosis. To determine the [...] Read more.

Acute abdominal pain (colic) is one of the major equine health threats worldwide and often necessitates intensive veterinary medical care and surgical intervention. Equine coronavirus (ECoV) infections can cause colic in horses but are rarely considered as a differential diagnosis. To determine the frequency of otherwise undetected ECoV infections in horses with acute colic, fresh fecal samples of 105 horses with acute colic and 36 healthy control horses were screened for viruses belonging to the Betacoronavirus 1 species by RT-PCR as well as for gastrointestinal helminths and bacteria commonly associated with colic. Horses with colic excreted significantly fewer strongyle eggs than horses without colic. The prevalence of anaerobic, spore-forming, gram-positive bacteria (Clostridium perfringens and Clostridioides difficile) was significantly higher in the feces of horses with colic. Six horses with colic (5.7%) and one horse from the control group (2.8%) tested positive for Betacoronaviruses. Coronavirus-positive samples were sequenced to classify the virus by molecular phylogeny (N gene). Interestingly, in three out of six coronavirus-positive horses with colic, sequences closely related to bovine coronaviruses (BCoV) were found. The pathogenic potential of BCoV in horses remains unclear and warrants further investigation. Full article

(This article belongs to the Special Issue Coronaviruses: Virology and Zoonotic Potential)

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23 pages, 3241 KB

Open AccessEditor’s ChoiceArticle

Brucella ceti Infection in Striped Dolphins from Italian Seas: Associated Lesions and Epidemiological Data

by Carla Grattarola, Antonio Petrella, Giuseppe Lucifora, Gabriella Di Francesco, Fabio Di Nocera, Antonio Pintore, Cristiano Cocumelli, Giuliana Terracciano, Antonio Battisti, Ludovica Di Renzo, Donatella Farina, Cristina Esmeralda Di Francesco, Maria Ines Crescio, Simona Zoppi, Alessandro Dondo, Barbara Iulini, Katia Varello, Walter Mignone, Maria Goria, Virginia Mattioda, Federica Giorda, Giovanni Di Guardo, Anna Janowicz, Manuela Tittarelli, Fabrizio De Massis, Cristina Casalone and Giuliano Garofolo Show full author list Hide full author list

Pathogens 2023, 12(8), 1034; https://doi.org/10.3390/pathogens12081034 - 13 Aug 2023

Cited by 17 | Viewed by 4930

Abstract

Brucella ceti infections have been increasingly reported in cetaceans. In this study, we analyzed all cases of B. ceti infection detected in striped dolphins stranded along the Italian coastline between 2012 and 2021 (N = 24). We focused on the pathogenic role [...] Read more.

Brucella ceti infections have been increasingly reported in cetaceans. In this study, we analyzed all cases of B. ceti infection detected in striped dolphins stranded along the Italian coastline between 2012 and 2021 (N = 24). We focused on the pathogenic role of B. ceti through detailed pathological studies, and ad hoc microbiological, biomolecular, and serological investigations, coupled with a comparative genomic analysis of the strains. Neurobrucellosis was observed in 20 animals. The primary histopathologic features included non-suppurative meningoencephalitis (N = 9), meningitis (N = 6), and meningoencephalomyelitis (N = 5), which was also associated with typical lesions in other tissues (N = 8). Co-infections were detected in more than half of the cases, mostly involving Cetacean Morbillivirus (CeMV). The 24 B. ceti isolates were assigned primarily to sequence type 26 (ST26) (N = 21) and, in a few cases, ST49 (N = 3). The multilocus sequence typing (cgMLST) based on whole genome sequencing (WGS) data showed that strains from Italy clustered into four genetically distinct clades. Plotting these clades onto a geographic map suggests a link between their phylogeny and the topographical distribution. These results support the role of B. ceti as a primary neurotropic pathogen for striped dolphins and highlight the utility of WGS data in understanding the evolution of this emerging pathogen. Full article

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

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16 pages, 2308 KB

Open AccessEditor’s ChoiceArticle

HLA-II-Dependent Neuroimmune Changes in Group A Streptococcal Necrotizing Fasciitis

by Ganesh Ambigapathy, Santhosh Mukundan, Kumi Nagamoto-Combs, Colin K. Combs and Suba Nookala

Pathogens 2023, 12(8), 1000; https://doi.org/10.3390/pathogens12081000 - 31 Jul 2023

Cited by 2 | Viewed by 2774

Abstract

Streptococcus pyogenes (Group A Streptococcus, GAS) bacteria cause a spectrum of human diseases ranging from self-limiting pharyngitis and mild, uncomplicated skin infections (impetigo, erysipelas, and cellulitis) to highly morbid and rapidly invasive, life-threatening infections such as streptococcal toxic shock syndrome and necrotizing fasciitis [...] Read more.

Streptococcus pyogenes (Group A Streptococcus, GAS) bacteria cause a spectrum of human diseases ranging from self-limiting pharyngitis and mild, uncomplicated skin infections (impetigo, erysipelas, and cellulitis) to highly morbid and rapidly invasive, life-threatening infections such as streptococcal toxic shock syndrome and necrotizing fasciitis (NF). HLA class II allelic polymorphisms are linked with differential outcomes and severity of GAS infections. The dysregulated immune response and peripheral cytokine storm elicited due to invasive GAS infections increase the risk for toxic shock and multiple organ failure in genetically susceptible individuals. We hypothesized that, while the host immune mediators regulate the immune responses against peripheral GAS infections, these interactions may simultaneously trigger neuropathology and, in some cases, induce persistent alterations in the glial phenotypes. Here, we studied the consequences of peripheral GAS skin infection on the brain in an HLA-II transgenic mouse model of GAS NF with and without treatment with an antibiotic, clindamycin (CLN). Mice expressing the human HLA-II DR3 (DR3) or the HLA-II DR4 (DR4) allele were divided into three groups: (i) uninfected controls, (ii) subcutaneously infected with a clinical GAS strain isolated from a patient with GAS NF, and (iii) GAS-infected with CLN treatment (10 mg/kg/5 days, intraperitoneal). The groups were monitored for 15 days post-infection. Skin GAS burden and lesion area, splenic and hippocampal mRNA levels of inflammatory markers, and immunohistochemical changes in hippocampal GFAP and Iba-1 immunoreactivity were assessed. Skin GAS burden and hippocampal mRNA levels of the inflammatory markers S100A8/A9, IL-1β, IL-33, inflammasome-related caspase-1 (Casp1), and NLRP6 were elevated in infected DR3 but not DR4 mice. The levels of these markers were significantly reduced following CLN treatment in DR3 mice. Although GAS was not detectable in the brain, astrocyte (GFAP) and microglia (Iba-1) activation were evident from increased GFAP and Iba-1 mRNA levels in DR3 and DR4 mice. However, CLN treatment significantly reduced GFAP mRNA levels in DR3 mice, not DR4 mice. Our data suggest a skin–brain axis during GAS NF, demonstrating that peripherally induced pathological conditions regulate neuroimmune changes and gliotic events in the brain. Full article

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14 pages, 1528 KB

Open AccessEditor’s ChoiceArticle

Dynamics of Infections in Cattle and Rhipicephalus microplus: A Preliminary Study

by Elianne Piloto-Sardiñas, Angélique Foucault-Simonin, Alejandra Wu-Chuang, Lourdes Mateos-Hernández, Roxana Marrero-Perera, Lianet Abuin-Denis, Lisset Roblejo-Arias, Cristian Díaz-Corona, Zbigniew Zając, Joanna Kulisz, Aneta Woźniak, Sara Moutailler, Belkis Corona-González and Alejandro Cabezas-Cruz

Pathogens 2023, 12(8), 998; https://doi.org/10.3390/pathogens12080998 - 30 Jul 2023

Cited by 7 | Viewed by 2958

Abstract

Tick-borne pathogens (TBPs) pose a significant threat to livestock, including bovine species. This study aimed to investigate TBPs in cattle and ticks across four sampling points, utilizing real-time microfluidic PCR. The results revealed that Rhipicephalus microplus ticks were found infesting all animals. Among [...] Read more.

Tick-borne pathogens (TBPs) pose a significant threat to livestock, including bovine species. This study aimed to investigate TBPs in cattle and ticks across four sampling points, utilizing real-time microfluidic PCR. The results revealed that Rhipicephalus microplus ticks were found infesting all animals. Among the detected TBPs in cattle, Anaplasma marginale was the most frequently identified, often as a single infection, although mixed infections involving Rickettsia felis, uncharacterized Rickettsia sp., and Anaplasma sp. were also observed. In ticks, A. marginale was predominant, along with R. felis, Rickettsia sp., and Ehrlichia sp. It is noteworthy that although A. marginale consistently infected all cattle during various sampling times, this pathogen was not detected in all ticks. This suggests a complex dynamic of pathogen acquisition by ticks. A phylogenetic analysis focused on the identification of Anaplasma species using amplified 16S rDNA gene fragments revealed the presence of A. marginale and Anaplasma platys strains in bovines. These findings underscore the presence of multiple TBPs in both cattle and ticks, with A. marginale being the most prevalent. Understanding the dynamics and phylogenetics of TBPs is crucial for developing effective control strategies to mitigate tick-borne diseases in livestock. Full article

(This article belongs to the Collection Advances in Tick Research)

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14 pages, 3549 KB

Open AccessEditor’s ChoiceArticle

Genomic Analysis of Yersinia pestis Strains from Brazil: Search for Virulence Factors and Association with Epidemiological Data

by João Luiz de Lemos Padilha Pitta, Matheus Filgueira Bezerra, Diego Leandro Reis da Silva Fernandes, Tessa de Block, Ane de Souza Novaes, Alzira Maria Paiva de Almeida and Antonio Mauro Rezende

Pathogens 2023, 12(8), 991; https://doi.org/10.3390/pathogens12080991 - 28 Jul 2023

Cited by 5 | Viewed by 3347

Abstract

Yersinia pestis, the etiological agent of the plague, is considered a genetically homogeneous species. Brazil is currently in a period of epidemiological silence but plague antibodies are still detected in sentinel animals, suggesting disease activity in the sylvatic cycle. The present study [...] Read more.

Yersinia pestis, the etiological agent of the plague, is considered a genetically homogeneous species. Brazil is currently in a period of epidemiological silence but plague antibodies are still detected in sentinel animals, suggesting disease activity in the sylvatic cycle. The present study deployed an in silico approach to analyze virulence factors among 407 Brazilian genomes of Y. pestis belonging to the Fiocruz Collection (1966–1997). The pangenome analysis associated several known virulence factors of Y. pestis in clades according to the presence or absence of genes. Four main strain clades (C, E, G, and H) exhibited the absence of various virulence genes. Notably, clade G displayed the highest number of absent genes, while clade E showed a significant absence of genes related to the T6SS secretion system and clade H predominantly demonstrated the absence of plasmid-related genes. These results suggest attenuation of virulence in these strains over time. The cgMLST analysis associated genomic and epidemiological data highlighting evolutionary patterns related to the isolation years and outbreaks of Y. pestis in Brazil. Thus, the results contribute to the understanding of the genetic diversity and virulence within Y. pestis and the potential for utilizing genomic data in epidemiological investigations. Full article

(This article belongs to the Special Issue An Ancient Terror, Yersinia pestis: What's New?)

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12 pages, 1621 KB

Open AccessEditor’s ChoiceArticle

Trends from the Last Decade with Nontuberculous Mycobacteria Lung Disease (NTM-LD): Clinicians’ Perspectives in Regional Center of Pulmonology in Bydgoszcz, Poland

by Grzegorz Przybylski, Jakub Bukowski, Weronika Kowalska, Marta Pilaczyńska-Cemel and Dorota Krawiecka

Pathogens 2023, 12(8), 988; https://doi.org/10.3390/pathogens12080988 - 28 Jul 2023

Cited by 8 | Viewed by 3243

Abstract

Background: Nontuberculous mycobacteria (NTM) are the cause of chronic lung disease called NTM lung disease (NTM-LD). There are about 180 known species of NTM. Nowadays the number of NTM-LD is increasing. Objective: To evaluate the clinical significance of NTM isolated from specimens and [...] Read more.

Background: Nontuberculous mycobacteria (NTM) are the cause of chronic lung disease called NTM lung disease (NTM-LD). There are about 180 known species of NTM. Nowadays the number of NTM-LD is increasing. Objective: To evaluate the clinical significance of NTM isolated from specimens and assess the frequency and clinical relevance of isolation of NTM in the Regional Center of Pulmonology in Bydgoszcz, hospital of Northern Poland. Design: Clinical, radiological, and microbiological data were collected from all patients from whom NTM was isolated between 2013 and 2022. Data were reviewed retrospectively. Diagnostic criteria for NTM-LD published by the American Thoracic Society (ATS) were used to determine clinical relevance. Material and methods: The study comprised 81,985 clinical specimens submitted for mycobacterial culture in the Department of Microbiology at the Regional Center of Pulmonology in Bydgoszcz between 2013 and 2022. Clinical specimens were processed according to the standard procedure in mycobacteria laboratories in Poland. NTM strains were identified using analysis of mycolic acids by chromatography as well as GenoType NTM-DR, GenoType Mycobacterium AS, and GenoType Mycobacterium CM. Results: There were 395 patients with NTM strains between 2013 and 2022. Out of them, 149 cases met the diagnostic criteria of NTM-LD and were classified as definite cases. M. kansasii (n = 77) was the most common species in the group (51.68%), followed by M. avium complex (n = 46). Patients with NTM-LD were 22–88 years old (median age was 60 years). There were 81 men and 68 women. The most common symptoms were cough, hemoptysis, and fever. Radiological X-ray images were dominated by infiltrative lesions in the upper and middle lobe of the right lung with cavities; the changes were in the upper lobe of the left lung and on both sides of the chest. They were smokers in 61%. The most common concomitant diseases were chronic obstructive pulmonary disease (COPD), diabetes mellitus, pulmonary carcinoma, and human immunodeficiency virus (HIV) infection, and other immunodeficiencies. The most common treatment was isoniazid, ethambutol, rifampicin, and ofloxacin for 18 months with a minimum of 12 months of culture negativity. Conclusions: NTM-LD infections are present with other pulmonary illnesses and extrapulmonary diseases and may be connected to primary immunologic deficiencies. These diseases concern patients of all ages and have various clinical manifestations. M. kansasii and MAC are the most prevalent NTM isolates among respiratory samples in Northern Poland. In addition, an increase in MAC and a decrease in M. kansasii both in cultivation and the cause of NTM-LD were reported. Full article

(This article belongs to the Special Issue Recent Advances in Nontuberculous Mycobacteria (NTM))

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15 pages, 4500 KB

Open AccessEditor’s ChoiceArticle

Establishment of a Nipah Virus Disease Model in Hamsters, including a Comparison of Intranasal and Intraperitoneal Routes of Challenge

by Stephen Findlay-Wilson, Lucy Flett, Francisco J. Salguero, Ines Ruedas-Torres, Susan Fotheringham, Linda Easterbrook, Victoria Graham and Stuart Dowall

Pathogens 2023, 12(8), 976; https://doi.org/10.3390/pathogens12080976 - 26 Jul 2023

Cited by 8 | Viewed by 2977

Abstract

Nipah virus (NiV) is an emerging pathogen that can cause severe respiratory illness and encephalitis in humans. The main reservoir is fruit bats, distributed across a large geographical area that includes Australia, Southeast Asia, and Africa. Incursion into humans is widely reported through [...] Read more.

Nipah virus (NiV) is an emerging pathogen that can cause severe respiratory illness and encephalitis in humans. The main reservoir is fruit bats, distributed across a large geographical area that includes Australia, Southeast Asia, and Africa. Incursion into humans is widely reported through exposure of infected pigs, ingestion of contaminated food, or through contact with an infected person. With no approved treatments or vaccines, NiV poses a threat to human public health and has epidemic potential. To aid with the assessment of emerging interventions being developed, an expansion of preclinical testing capability is required. Given variations in the model parameters observed in different sites during establishment, optimisation of challenge routes and doses is required. Upon evaluating the hamster model, an intranasal route of challenge was compared with intraperitoneal delivery, demonstrating a more rapid dissemination to wider tissues in the latter. A dose effect was observed between those causing respiratory illness and those resulting in neurological disease. The data demonstrate the successful establishment of the hamster model of NiV disease for subsequent use in the evaluation of vaccines and antivirals. Full article

(This article belongs to the Special Issue Emerging Viruses and Viral Zoonoses)

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13 pages, 286 KB

Open AccessEditor’s ChoiceReview

The Importance of the One Health Concept in Combating Zoonoses

by Elina Horefti

Pathogens 2023, 12(8), 977; https://doi.org/10.3390/pathogens12080977 - 26 Jul 2023

Cited by 32 | Viewed by 6873

Abstract

One Health fundamentally acknowledges that human health is linked to animal health and the environment. One of the pillars One Health is built on is zoonoses. Through the years, zoonotic infections have caused numerous outbreaks and pandemics, as well as millions of fatalities, [...] Read more.

One Health fundamentally acknowledges that human health is linked to animal health and the environment. One of the pillars One Health is built on is zoonoses. Through the years, zoonotic infections have caused numerous outbreaks and pandemics, as well as millions of fatalities, with the COVID-19 pandemic being the latest one. Apart from the consequences to public health, zoonoses also affect society and the economy. Since its establishment, One Health has contributed significantly to the protection of humans, animals, and the environment, through preparedness, surveillance, and mitigation of such public dangers. Full article

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

17 pages, 2077 KB

Open AccessEditor’s ChoiceArticle

Corynebacterium ulcerans Infections in Eurasian Beavers (Castor fiber)

by Reinhard Sting, Catharina Pölzelbauer, Tobias Eisenberg, Rebecca Bonke, Birgit Blazey, Martin Peters, Karin Riße, Andreas Sing, Anja Berger, Alexandra Dangel and Jörg Rau

Pathogens 2023, 12(8), 979; https://doi.org/10.3390/pathogens12080979 - 26 Jul 2023

Cited by 5 | Viewed by 2691

Abstract

The Eurasian beaver (Castor fiber) has been reintroduced successfully in Germany since the 1990s. Since wildlife is an important source of zoonotic infectious diseases, monitoring of invasive and reintroduced species is crucial with respect to the One Health approach. Three Eurasian beavers [...] Read more.

The Eurasian beaver (Castor fiber) has been reintroduced successfully in Germany since the 1990s. Since wildlife is an important source of zoonotic infectious diseases, monitoring of invasive and reintroduced species is crucial with respect to the One Health approach. Three Eurasian beavers were found dead in the German federal states of Bavaria, North Rhine–Westphalia and Baden–Wuerttemberg in 2015, 2021 and 2022, respectively. During post-mortem examinations, Corynebacterium (C.) ulcerans could be isolated from the abscesses of two beavers and from the lungs of one of the animals. Identification of the bacterial isolates at the species level was carried out by spectroscopic analysis using MALDI-TOF MS, FT-IR and biochemical profiles and were verified by molecular analysis based on 16-23S internal transcribed spacer (ITS) region sequencing. Molecular characterization of the C. ulcerans isolates using whole-genome sequencing (WGS) revealed a genome size of about 2.5 Mbp and a GC content of 53.4%. Multilocus sequence typing (MLST) analysis classified all three isolates as the sequence type ST-332. A minimum spanning tree (MST) based on cgMLST allelic profiles, including 1211 core genes of the sequenced C. ulcerans isolates, showed that the beaver-derived isolates clearly group on the branch of C. ulcerans with the closest relationship to each other, in close similarity to an isolate from a dog. Antibiotic susceptibility testing revealed resistance to clindamycin and, in one strain, to erythromycin according to EUCAST, while all isolates were susceptible to the other antimicrobials tested. Full article

(This article belongs to the Special Issue Emerging Zoonoses: The Bridge Between Human and Animal Diseases in the One Health Paradigm)

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20 pages, 1592 KB

Open AccessEditor’s ChoiceArticle

Assessing Onchocerca volvulus Intensity of Infection and Genetic Diversity Using Mitochondrial Genome Sequencing of Single Microfilariae Obtained before and after Ivermectin Treatment

by Shannon M. Hedtke, Young-Jun Choi, Anusha Kode, Gowtam C. Chalasani, Neha Sirwani, Stephen R. Jada, An Hotterbeekx, Michel Mandro, Joseph N. Siewe Fodjo, Glory Ngongeh Amambo, Raphael A. Abong, Samuel Wanji, Annette C. Kuesel, Robert Colebunders, Makedonka Mitreva and Warwick N. Grant

Pathogens 2023, 12(7), 971; https://doi.org/10.3390/pathogens12070971 - 24 Jul 2023

Cited by 7 | Viewed by 3095

Abstract

Onchocerciasis is a neglected tropical disease targeted for elimination using ivermectin mass administration. Ivermectin kills the microfilariae and temporarily arrests microfilariae production by the macrofilariae. We genotyped 436 microfilariae from 10 people each in Ituri, Democratic Republic of the Congo (DRC), and Maridi [...] Read more.

Onchocerciasis is a neglected tropical disease targeted for elimination using ivermectin mass administration. Ivermectin kills the microfilariae and temporarily arrests microfilariae production by the macrofilariae. We genotyped 436 microfilariae from 10 people each in Ituri, Democratic Republic of the Congo (DRC), and Maridi County, South Sudan, collected before and 4–5 months after ivermectin treatment. Population genetic analyses identified 52 and 103 mitochondrial DNA haplotypes among the microfilariae from DRC and South Sudan, respectively, with few haplotypes shared between people. The percentage of genotype-based correct assignment to person within DRC was ~88% and within South Sudan ~64%. Rarefaction and extrapolation analysis showed that the genetic diversity in DRC, and even more so in South Sudan, was captured incompletely. The results indicate that the per-person adult worm burden is likely higher in South Sudan than DRC. Analyses of haplotype data from a subsample (n = 4) did not discriminate genetically between pre- and post-treatment microfilariae, confirming that post-treatment microfilariae are not the result of new infections. With appropriate sampling, mitochondrial haplotype analysis could help monitor changes in the number of macrofilariae in a population as a result of treatment, identify cases of potential treatment failure, and detect new infections as an indicator of continuing transmission. Full article

(This article belongs to the Section Parasitic Pathogens)

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22 pages, 13797 KB

Open AccessEditor’s ChoiceArticle

Art of the Kill: Designing and Testing Viral Inactivation Procedures for Highly Pathogenic Negative Sense RNA Viruses

by Judith Olejnik, Adam J. Hume, Stephen J. Ross, Whitney A. Scoon, Scott Seitz, Mitchell R. White, Ben Slutzky, Nadezhda E. Yun and Elke Mühlberger

Pathogens 2023, 12(7), 952; https://doi.org/10.3390/pathogens12070952 - 19 Jul 2023

Cited by 9 | Viewed by 6548

Abstract

The study of highly pathogenic viruses handled under BSL-4 conditions and classified as Select Agents frequently involves the transfer of inactivated materials to lower containment levels for downstream analyses. Adhering to Select Agent and BSL-4 safety regulations requires validation or verification of the [...] Read more.

The study of highly pathogenic viruses handled under BSL-4 conditions and classified as Select Agents frequently involves the transfer of inactivated materials to lower containment levels for downstream analyses. Adhering to Select Agent and BSL-4 safety regulations requires validation or verification of the inactivation procedures, which comes with an array of challenges for each method. This includes the use of cytotoxic reagents for chemical inactivation and defining the precise inactivation parameters for physical inactivation. Here, we provide a workflow for various inactivation methods using Ebola, Nipah, and Lassa viruses as our examples. We choose three distinct inactivation methods (TRIzol/TRIzol LS, aldehyde fixation using different fixatives, and heat) to highlight the challenges of each method and provide possible solutions. We show that, whereas published chemical inactivation methods are highly reliable, the parameters for heat inactivation must be clearly defined to ensure complete inactivation. In addition to the inactivation data, we also provide examples and templates for the documentation required for approval and use of inactivation SOPs, including an inactivation report, the procedure sections of developed SOPs, and an electronic inactivation certificate that accompanies inactivated samples. The provided information can be used as a roadmap for similar studies at high and maximum containment laboratories. Full article

(This article belongs to the Special Issue Editorial Board Members’ Collection Series: Molecular Epidemiology, Diagnostics and Management of Viral Pathogens)

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9 pages, 474 KB

Open AccessEditor’s ChoiceArticle

Evaluation of Lipid Profile and Intima Media Thickness in Antiretroviral-Experienced HIV-Infected Patients Treated with Protease Inhibitor-Based Regimens versus Protease Inhibitor-Sparing Regimens

by Salvatore Martini, Mariantonietta Pisaturo, Antonio Russo, Maria Grazia Palamone, Maria Teresa Russo, Verdiana Zollo, Paolo Maggi and Nicola Coppola

Pathogens 2023, 12(7), 925; https://doi.org/10.3390/pathogens12070925 - 10 Jul 2023

Cited by 7 | Viewed by 1885

Abstract

Background: Antiretroviral therapy has increasingly improved management of HIV infection, ensuring long-term efficacy and tolerability. Each class of antiretrovirals has, however, different characteristics and different tolerability profiles. The literature data show that protease inhibitors (PIs) are associated with a higher incidence of dyslipidemia. [...] Read more.

Background: Antiretroviral therapy has increasingly improved management of HIV infection, ensuring long-term efficacy and tolerability. Each class of antiretrovirals has, however, different characteristics and different tolerability profiles. The literature data show that protease inhibitors (PIs) are associated with a higher incidence of dyslipidemia. The aim of our study was to evaluate whether patients treated with PIs have both greater dyslipidemia and increased intima media thickness (IMT) and atheromatous plaques compared to patients treated without PIs. Materials and Methods: A total of 110 HIV-experienced patients screened with Doppler ultrasonography of the supra-aortic trunks in December 2019 were enrolled in a retrospective cross-sectional observational study. Patients were divided into two groups: 59 in the PI-based group, treated with PIs, and 51 in the PI-sparing group. In the two groups, we evaluated lipids, cardiovascular risk factors (smoking, BMI, age, hypertension), increased pathological IMT (a value > 1 mm), and possible atheromatous plaque. Results: Serum LDL (p 0.04) and percentage of patients with hypercholesterolemia (p 0.03) were higher in the PI-based than in the PI-sparing group. Doppler data showed a trend in increase of IMT > 1 in the PI-based group, which appeared statistically significant for the section of the left common carotid artery (p 0.03). However, in multivariate logistic regression models, none of the evaluated variables were significantly associated with IMT > 1. Conclusions: Our real-life data show that patients treated with PIs have a trend of developing both greater dyslipidemia and increased pathological IMT and atheromatous plaques These findings may be useful to optimize antiretrovirals for patients with cardiovascular risk factors. Full article

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

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20 pages, 2738 KB

Open AccessEditor’s ChoiceArticle

Helminths in Invasive Raccoons (Procyon lotor) from Southwest Germany

by Nico P. Reinhardt, Marion Wassermann, Jessica Härle, Thomas Romig, Lina Kurzrock, Janosch Arnold, Ernst Großmann, Ute Mackenstedt and Reinhard K. Straubinger

Pathogens 2023, 12(7), 919; https://doi.org/10.3390/pathogens12070919 - 8 Jul 2023

Cited by 7 | Viewed by 3320

Abstract

As hosts of numerous zoonotic pathogens, the role of raccoons needs to be considered in the One Health context. Raccoons progressively expand their range as invasive alien species in Europe. This study aimed to investigate the intestinal helminth fauna of raccoons in Baden-Wuerttemberg, [...] Read more.

As hosts of numerous zoonotic pathogens, the role of raccoons needs to be considered in the One Health context. Raccoons progressively expand their range as invasive alien species in Europe. This study aimed to investigate the intestinal helminth fauna of raccoons in Baden-Wuerttemberg, Germany, as no such screening had ever been conducted there. In total, we obtained 102 animals from hunters in 2019 and 2020. Intestinal helminths were retrieved using the SSCT (segmented sedimentation and counting technique) and identified morphologically and by PCR-based Sanger sequencing. Fecal samples were assessed using the ELISA PetChek^TM IP assay (IDEXX, Germany) and flotation technique. The artificial digestion method was employed for analyzing muscle tissue. We detected species of four nematode genera (Baylisascaris procyonis, Toxocara canis, Capillaria spp., and Trichuris spp.), three cestode genera (Atriotaenia cf. incisa/procyonis, Taenia martis, and Mesocestoides spp.), and three trematode genera (Isthmiophora hortensis/melis, Plagiorchis muris, and Brachylaima spp.). Echinococcus spp. and Trichinella spp. were not found. The invasive behavior and synanthropic habits of raccoons may increase the infection risk with these helminths in wildlife, domestic and zoo animals, and humans by serving as a connecting link. Therefore, it is crucial to initiate additional studies assessing these risks. Full article

(This article belongs to the Special Issue Helminth Infection and Molecular Identification in Wild and Domestic Animals)

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14 pages, 1942 KB

Open AccessEditor’s ChoiceArticle

Role of D(−)-Lactic Acid in Prevention of Chlamydia trachomatis Infection in an In Vitro Model of HeLa Cells

by Chiara Zalambani, Nicola Rizzardi, Giacomo Marziali, Claudio Foschi, Sara Morselli, Marielle Ezekielle Djusse, Marina Naldi, Romana Fato, Natalia Calonghi and Antonella Marangoni

Pathogens 2023, 12(7), 883; https://doi.org/10.3390/pathogens12070883 - 28 Jun 2023

Cited by 7 | Viewed by 2643

Abstract

A vaginal microbiota dominated by certain Lactobacillus species may have a protective effect against Chlamydia trachomatis infection. One of the key antimicrobial compounds produced is lactic acid, which is believed to play a central role in host defense. Lactobacillus strains producing the D(−)-lactic [...] Read more.

A vaginal microbiota dominated by certain Lactobacillus species may have a protective effect against Chlamydia trachomatis infection. One of the key antimicrobial compounds produced is lactic acid, which is believed to play a central role in host defense. Lactobacillus strains producing the D(−)-lactic acid isomer are known to exert stronger protection. However, the molecular mechanisms underlying this antimicrobial action are not well understood. The aim of this study was to investigate the role of D(−)-lactic acid isomer in the prevention of C. trachomatis infection in an in vitro HeLa cell model. We selected two strains of lactobacilli belonging to different species: a vaginal isolate of Lactobacillus crispatus that releases both D(−) and L(+) isomers and a strain of Lactobacillus reuteri that produces only the L(+) isomer. Initially, we demonstrated that L. crispatus was significantly more effective than L. reuteri in reducing C. trachomatis infectivity. A different pattern of histone acetylation and lactylation was observed when HeLa cells were pretreated for 24 h with supernatants of Lactobacillus crispatus or L. reuteri, resulting in different transcription of genes such as CCND1, CDKN1A, ITAG5 and HER-1. Similarly, distinct transcription patterns were found in HeLa cells treated with 10 mM D(−)- or L(+)-lactic acid isomers. Our findings suggest that D(−) lactic acid significantly affects two non-exclusive mechanisms involved in C. trachomatis infection: regulation of the cell cycle and expression of EGFR and α5β1-integrin. Full article

(This article belongs to the Special Issue Chlamydia trachomatis: Innate Immunity, Vaccines and Behaviour)

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17 pages, 1705 KB

Open AccessEditor’s ChoiceArticle

Quantitative Risk Assessment of Oocyst Versus Bradyzoite Foodborne Transmission of Toxoplasma gondii in Brazil

by Sophie Zhu, Elizabeth VanWormer, Beatriz Martínez-López, Lílian Maria Garcia Bahia-Oliveira, Renato Augusto DaMatta, Pedro Souto Rodrigues and Karen Shapiro

Pathogens 2023, 12(7), 870; https://doi.org/10.3390/pathogens12070870 - 25 Jun 2023

Cited by 8 | Viewed by 3223

Abstract

Toxoplasma gondii is a globally distributed zoonotic protozoan parasite. Infection with T. gondii can cause congenital toxoplasmosis in developing fetuses and acute outbreaks in the general population, and the disease burden is especially high in South America. Prior studies found that the environmental [...] Read more.

Toxoplasma gondii is a globally distributed zoonotic protozoan parasite. Infection with T. gondii can cause congenital toxoplasmosis in developing fetuses and acute outbreaks in the general population, and the disease burden is especially high in South America. Prior studies found that the environmental stage of T. gondii, oocysts, is an important source of infection in Brazil; however, no studies have quantified this risk relative to other parasite stages. We developed a Bayesian quantitative risk assessment (QRA) to estimate the relative attribution of the two primary parasite stages (bradyzoite and oocyst) that can be transmitted in foods to people in Brazil. Oocyst contamination in fruits and greens contributed significantly more to overall estimated T. gondii infections than bradyzoite-contaminated foods (beef, pork, poultry). In sensitivity analysis, treatment, i.e., cooking temperature for meat and washing efficiency for produce, most strongly affected the estimated toxoplasmosis incidence rate. Due to the lack of regional food contamination prevalence data and the high level of uncertainty in many model parameters, this analysis provides an initial estimate of the relative importance of food products. Important knowledge gaps for oocyst-borne infections were identified and can drive future studies to improve risk assessments and effective policy actions to reduce human toxoplasmosis in Brazil. Full article

(This article belongs to the Special Issue Toxoplasma gondii and Food Safety)

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21 pages, 5354 KB

Open AccessEditor’s ChoiceArticle

Newly Designed Poxviral Promoters to Improve Immunogenicity and Efficacy of MVA-NP Candidate Vaccines against Lethal Influenza Virus Infection in Mice

by Martin C. Langenmayer, Anna-Theresa Luelf-Averhoff, Lisa Marr, Sylvia Jany, Astrid Freudenstein, Silvia Adam-Neumair, Alina Tscherne, Robert Fux, Juan J. Rojas, Andreas Blutke, Gerd Sutter and Asisa Volz

Pathogens 2023, 12(7), 867; https://doi.org/10.3390/pathogens12070867 - 23 Jun 2023

Cited by 6 | Viewed by 2626

Abstract

Influenza, a respiratory disease mainly caused by influenza A and B, viruses of the Orthomyxoviridae, is still a burden on our society’s health and economic system. Influenza A viruses (IAV) circulate in mammalian and avian populations, causing seasonal outbreaks with high numbers [...] Read more.

Influenza, a respiratory disease mainly caused by influenza A and B, viruses of the Orthomyxoviridae, is still a burden on our society’s health and economic system. Influenza A viruses (IAV) circulate in mammalian and avian populations, causing seasonal outbreaks with high numbers of cases. Due to the high variability in seasonal IAV triggered by antigenic drift, annual vaccination is necessary, highlighting the need for a more broadly protective vaccine against IAV. The safety tested Modified Vaccinia virus Ankara (MVA) is licensed as a third-generation vaccine against smallpox and serves as a potent vector system for the development of new candidate vaccines against different pathogens. Here, we generated and characterized recombinant MVA candidate vaccines that deliver the highly conserved internal nucleoprotein (NP) of IAV under the transcriptional control of five newly designed chimeric poxviral promoters to further increase the immunogenic properties of the recombinant viruses (MVA-NP). Infections of avian cell cultures with the recombinant MVA-NPs demonstrated efficient synthesis of the IAV-NP which was expressed under the control of the five new promoters. Prime-boost or single shot immunizations in C57BL/6 mice readily induced circulating serum antibodies’ binding to recombinant IAV-NP and the robust activation of IAV-NP-specific CD8+ T cell responses. Moreover, the MVA-NP candidate vaccines protected C57BL/6 mice against lethal respiratory infection with mouse-adapted IAV (A/Puerto Rico/8/1934/H1N1). Thus, further studies are warranted to evaluate the immunogenicity and efficacy of these recombinant MVA-NP vaccines in other IAV challenge models in more detail. Full article

(This article belongs to the Special Issue Animal Models for Human Viruses)

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16 pages, 2154 KB

Open AccessEditor’s ChoiceReview

The Importance of Measuring SARS-CoV-2-Specific T-Cell Responses in an Ongoing Pandemic

by Linda Petrone, Alessandro Sette, Rory D. de Vries and Delia Goletti

Pathogens 2023, 12(7), 862; https://doi.org/10.3390/pathogens12070862 - 22 Jun 2023

Cited by 25 | Viewed by 3356

Abstract

Neutralizing antibodies are considered a correlate of protection against SARS-CoV-2 infection and severe COVID-19, although they are not the only contributing factor to immunity: T-cell responses are considered important in protecting against severe COVID-19 and contributing to the success of vaccination effort. T-cell [...] Read more.

Neutralizing antibodies are considered a correlate of protection against SARS-CoV-2 infection and severe COVID-19, although they are not the only contributing factor to immunity: T-cell responses are considered important in protecting against severe COVID-19 and contributing to the success of vaccination effort. T-cell responses after vaccination largely mirror those of natural infection in magnitude and functional capacity, but not in breadth, as T-cells induced by vaccination exclusively target the surface spike glycoprotein. T-cell responses offer a long-lived line of defense and, unlike humoral responses, largely retain reactivity against the SARS-CoV-2 variants. Given the increasingly recognized role of T-cell responses in protection against severe COVID-19, the circulation of SARS-CoV-2 variants, and the potential implementation of novel vaccines, it becomes imperative to continuously monitor T-cell responses. In addition to “classical” T-cell assays requiring the isolation of peripheral blood mononuclear cells, simple whole-blood-based interferon-γ release assays have a potential role in routine T-cell response monitoring. These assays could be particularly useful for immunocompromised people and other clinically vulnerable populations, where interactions between cellular and humoral immunity are complex. As we continue to live alongside COVID-19, the importance of considering immunity as a whole, incorporating both humoral and cellular responses, is crucial. Full article

(This article belongs to the Collection SARS-CoV-2 Infection and COVID-19 Disease)

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19 pages, 2241 KB

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 6 | Viewed by 3091

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 KB

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

Cited by 2 | Viewed by 2656

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 KB

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 11 | Viewed by 9105

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 KB

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

Cited by 5 | Viewed by 4191

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 KB

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 11 | Viewed by 4127

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 KB

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

Cited by 5 | Viewed by 3070

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 KB

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 9 | Viewed by 4847

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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12 pages, 907 KB

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 - 8 Jun 2023

Cited by 14 | Viewed by 5274

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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15 pages, 1779 KB

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 - 8 Jun 2023

Cited by 8 | Viewed by 6822

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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11 pages, 2286 KB

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 - 4 Jun 2023

Cited by 2 | Viewed by 2085

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 KB

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 - 2 Jun 2023

Cited by 14 | Viewed by 6681

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 KB

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 - 1 Jun 2023

Cited by 9 | Viewed by 3958

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 KB

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 10 | Viewed by 7883

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 KB

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 7 | Viewed by 3243

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 KB

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 8 | Viewed by 5076

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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22 pages, 2064 KB

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 11 | Viewed by 6194

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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18 pages, 1641 KB

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 43 | Viewed by 9165

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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10 pages, 5234 KB

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

Cited by 1 | Viewed by 2562

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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