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Pathogens, Volume 11, Issue 7 (July 2022) – 109 articles

Cover Story (view full-size image): Bovine tuberculosis is a global infectious threat, with under-performance of current diagnostics being a huge challenge. After screening nine host proteins, we found that IL-2, CXCL-9, IP-10 and CCL4, like IFNγ, were significantly elevated in PPDb stimulated blood supernatants of M. bovis challenged cattle. Further assessment in various animal cohorts revealed that PPDb-specific IL-2 and IP-10, like IFNγ, could discriminate naive from M. bovis challenged cattle; and CCL4 showed a DIVA potential, i.e., differentiating Infected from BCG vaccinates. Combined analysis accurately identified M. bovis infection with strong correlations among PPDb-specific IFNγ, IL-2 and IP-10 levels. We provide proof of concept for utilizing multiple biomarker signatures for discriminating cattle based on M. bovis infection or BCG vaccination status. View this paper
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Article
Experimental Infection of Mice and Ticks with the Human Isolate of Anaplasma phagocytophilum NY-18
Pathogens 2022, 11(7), 820; https://doi.org/10.3390/pathogens11070820 - 21 Jul 2022
Viewed by 372
Abstract
Anaplasma phagocytophilum is the causative agent of tick-borne fever (TBF) and human granulocytic anaplasmosis (HGA) and is currently considered an emerging disease in the USA, Europe, and Asia. The increased prevalence of A. phagocytophilum as a human pathogen requires the detailed characterization of [...] Read more.
Anaplasma phagocytophilum is the causative agent of tick-borne fever (TBF) and human granulocytic anaplasmosis (HGA) and is currently considered an emerging disease in the USA, Europe, and Asia. The increased prevalence of A. phagocytophilum as a human pathogen requires the detailed characterization of human isolates and the implementation of appropriate animal models. In this study, we demonstrated that the dynamics of infection with the human isolate of A. phagocytophilum NY-18 was variable in three different strains of mice (SCID, C3H/HeN, BALB/c). We further evaluated the ability of Ixodes ricinus to acquire and transmit A. phagocytophilum NY-18 and compared it with Ixodes scapularis. Larvae of both tick species effectively acquired the pathogen while feeding on infected mice. The infection rates then decreased during the development to nymphs. Interestingly, molted I. ricinus nymphs were unable to transmit the pathogen to naïve mice, which contrasted with I. scapularis. The results of our study suggest that I. ricinus is not a competent vector for the American human Anaplasma isolate. Further studies are needed to establish reliable transmission models for I. ricinus and European human isolate(s) of A. phagocytophilum. Full article
(This article belongs to the Special Issue Ixodes ricinus and Disease Transmission)
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Review
The Current Knowledge on Clostridioides difficile Infection in Patients with Inflammatory Bowel Diseases
Pathogens 2022, 11(7), 819; https://doi.org/10.3390/pathogens11070819 - 21 Jul 2022
Viewed by 310
Abstract
Clostridioides difficile (C. difficile) represents a major health burden with substantial economic and clinical impact. Patients with inflammatory bowel diseases (IBD) were identified as a risk category for Clostridioides difficile infection (CDI). In addition to traditional risk factors for C. difficile [...] Read more.
Clostridioides difficile (C. difficile) represents a major health burden with substantial economic and clinical impact. Patients with inflammatory bowel diseases (IBD) were identified as a risk category for Clostridioides difficile infection (CDI). In addition to traditional risk factors for C. difficile acquisition, IBD-specific risk factors such as immunosuppression, severity and extension of the inflammatory disease were identified. C. difficile virulence factors, represented by both toxins A and B, induce the damage of the intestinal mucosa and vascular changes, and promote the inflammatory host response. Given the potential life-threatening complications, early diagnostic and therapeutic interventions are required. The screening for CDI is recommended in IBD exacerbations, and the diagnostic algorithm consists of clinical evaluation, enzyme immunoassays (EIAs) or nucleic acid amplification tests (NAATs). An increased length of hospitalization, increased colectomy rate and mortality are the consequences of concurrent CDI in IBD patients. Selection of CD strains of higher virulence, antibiotic resistance, and the increasing rate of recurrent infections make the management of CDI in IBD more challenging. An individualized therapeutic approach is recommended to control CDI as well as IBD flare. Novel therapeutic strategies have been developed in recent years in order to manage severe, refractory or recurrent CDI. In this article, we aim to review the current evidence in the field of CDI in patients with underlying IBD, pointing to pathogenic mechanisms, risk factors for infection, diagnostic steps, clinical impact and outcomes, and specific management. Full article
(This article belongs to the Special Issue Gastrointestinal Pathogens in Inflammatory Bowel Disease)
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Review
SUMOylation and Viral Infections of the Brain
Pathogens 2022, 11(7), 818; https://doi.org/10.3390/pathogens11070818 - 21 Jul 2022
Viewed by 379
Abstract
The small ubiquitin-like modifier (SUMO) system regulates numerous biological processes, including protein localization, stability and/or activity, transcription, and DNA repair. SUMO also plays critical roles in innate immunity and antiviral defense by mediating interferon (IFN) synthesis and signaling, as well as the expression [...] Read more.
The small ubiquitin-like modifier (SUMO) system regulates numerous biological processes, including protein localization, stability and/or activity, transcription, and DNA repair. SUMO also plays critical roles in innate immunity and antiviral defense by mediating interferon (IFN) synthesis and signaling, as well as the expression and function of IFN-stimulated gene products. Viruses including human immunodeficiency virus-1, Zika virus, herpesviruses, and coronaviruses have evolved to exploit the host SUMOylation system to counteract the antiviral activities of SUMO proteins and to modify their own proteins for viral persistence and pathogenesis. Understanding the exploitation of SUMO is necessary for the development of effective antiviral therapies. This review summarizes the interplay between viruses and the host SUMOylation system, with a special emphasis on viruses with neuro-invasive properties that have pathogenic consequences on the central nervous system. Full article
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Article
Variability among the Isolates of Broad Bean Mottle Virus and Encapsidation of Host RNAs
Pathogens 2022, 11(7), 817; https://doi.org/10.3390/pathogens11070817 - 21 Jul 2022
Viewed by 299
Abstract
Broad bean mottle bromovirus infects legume plants and is transmissible by insects. Several broad bean mottle virus (BBMV) isolates have been identified, including one in England (isolate Ba) and five in the Mediterranean countries: Libya (LyV), Morocco (MV), Syria (SV), Sudan (TU) and [...] Read more.
Broad bean mottle bromovirus infects legume plants and is transmissible by insects. Several broad bean mottle virus (BBMV) isolates have been identified, including one in England (isolate Ba) and five in the Mediterranean countries: Libya (LyV), Morocco (MV), Syria (SV), Sudan (TU) and Tunisia (TV). Previously, we analyzed the nucleotide sequence of the Ba RNA and here we report on and compare it with another five Mediterranean variants. The RNA segments in the latter ones were extensively homologous, with some SNPs, single nucleotide deletions and insertions, while the number of mutations was higher in isolate Ba. Both the 5′ and 3′ untranslated terminal regions (UTRs) among the corresponding RNAs are highly conserved, reflecting their functionality in virus replication. The AUG initiation codons are within suboptimal contexts, possibly to adjust/regulate translation. The proteins 1a, 2a, 3a and coat protein (CP) are almost identical among the five isolates, but in Ba they have more amino acid (aa) substitutions. Phylogenetic analysis revealed the isolates from Morocco and Syria clustering with the isolate from England, while the variants from Libya, Tunisia and Sudan created a different clade. The BBMV isolates encapsidate a high content of host (ribosomal and messenger) RNAs. Our studies present BBMV as a useful model for bromoviruses infecting legumes. Full article
(This article belongs to the Special Issue 10th Anniversary of Pathogens—Feature Papers)
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Review
COVID-19 as Another Trigger for HBV Reactivation: Clinical Case and Review of Literature
Pathogens 2022, 11(7), 816; https://doi.org/10.3390/pathogens11070816 - 21 Jul 2022
Viewed by 386
Abstract
Universal hepatitis B virus (HBV) vaccination has been applied for years in most countries, but HBV infection remains an unresolved public health problem worldwide, with over one-third of the world’s population infected during their lifetime and approximately 248 million hepatitis B surface antigen [...] Read more.
Universal hepatitis B virus (HBV) vaccination has been applied for years in most countries, but HBV infection remains an unresolved public health problem worldwide, with over one-third of the world’s population infected during their lifetime and approximately 248 million hepatitis B surface antigen (HBsAg) chronic carriers. HBV infection may reactivate with symptomatic and sometimes life-threatening clinical manifestations due to a reduction in the immune response of various origins, due to chemotherapy or immunosuppressive therapy, treatments increasingly practiced worldwide. SARS-CoV-2 and its COVID-19 associated disease have introduced new chances for HBV reactivation due to the use of dexamethasone and tocilizumab to counteract the cytokine storm. This could and should be prevented by accurate screening of HBV serologic markers and adequate pharmacologic prophylaxis. This article describes the case of a patient with COVID-19 who developed HBV reactivation and died of liver failure and analyzes published data on this setting to provide useful information to physicians who manage these patients during the SARS-CoV-2 pandemic. Full article
(This article belongs to the Special Issue Viral Hepatitis: The New Challenge in the Era of Antiviral Treatments)
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Case Report
A Ruptured Left Gastric Artery Aneurysm That Neoplasticized during the Course of Coronavirus Disease 2019: A Case Report
Pathogens 2022, 11(7), 815; https://doi.org/10.3390/pathogens11070815 - 20 Jul 2022
Viewed by 368
Abstract
Coronavirus disease 2019 (COVID-19) is an acute respiratory syndrome caused by SARS-CoV-2 and is known to cause respiratory and systemic symptoms. A SARS-CoV-2 infection is involved in aneurysm formation, enlargement, and rupture in medium-sized vessels, such as the cerebral and coronary arteries and [...] Read more.
Coronavirus disease 2019 (COVID-19) is an acute respiratory syndrome caused by SARS-CoV-2 and is known to cause respiratory and systemic symptoms. A SARS-CoV-2 infection is involved in aneurysm formation, enlargement, and rupture in medium-sized vessels, such as the cerebral and coronary arteries and the aorta. In contrast, its involvement in forming aneurysms in medium-sized vessels other than the cerebral and coronary arteries has not been reported. An 84-year-old Japanese man with COVID-19 was admitted to our hospital. The treatment course was favorable, and the COVID-19 treatment was completed by the 10th day. On day 14, pancreatic enzymes increased mildly. An abdominal computed tomography revealed a ruptured left gastric aneurysm after spontaneous hemostasis. Arterial embolization was performed. In this patient, a new left gastric aneurysm was suspected of having formed and ruptured during the course of the COVID-19 treatment. To the best of our knowledge, this is the first report of abdominal visceral aneurysm formation caused by COVID-19 in a medium-sized vessel, and it is necessary to remember that aneurysms can be formed at any site when treating this syndrome. Full article
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Article
The Biological Properties of the SARS-CoV-2 Cameroon Variant Spike: An Intermediate between the Alpha and Delta Variants
Pathogens 2022, 11(7), 814; https://doi.org/10.3390/pathogens11070814 - 20 Jul 2022
Viewed by 336
Abstract
An analysis of the structural effect of the mutations of the B.1.640.2 (IHU) Spike Receptor Binding Domain (RBD) and N-terminal Domain (NTD) is reported along with a comparison with the sister lineage B.1.640.1. and a selection of variants of concern. The effect of [...] Read more.
An analysis of the structural effect of the mutations of the B.1.640.2 (IHU) Spike Receptor Binding Domain (RBD) and N-terminal Domain (NTD) is reported along with a comparison with the sister lineage B.1.640.1. and a selection of variants of concern. The effect of the mutations on the RBD–ACE2 interaction was also assessed. The structural analysis applied computational methods that are able to carry out in silico mutagenesis to calculate energy minimization and the folding energy variation consequent to residue mutations. Tools for electrostatic calculation were applied to quantify and display the protein surface electrostatic potential. Interactions at the RBD–ACE2 interface were scrutinized using computational tools that identify the interactions and predict the contribution of each interface residue to the stability of the complex. The comparison among the RBDs shows that the most evident differences between the variants is in the distribution of the surface electrostatic potential: that of B.1.640.1 is as that of the Alpha RBD, while B.1.640.2 appears to have an intermediate surface potential pattern with characteristics between those of the Alpha and Delta variants. Moreover, the B.1.640.2 Spike includes the mutation E484K that in other variants has been suggested to be involved in immune evasion. These properties may hint at the possibility that B.1.640.2 emerged with a potentially increased infectivity with respect to the sister B.1.640.1 variant, but significantly lower than that of the Delta and Omicron variants. However, the analysis of their NTD domains highlights deletions, destabilizing mutations and charge alterations that can limit the ability of the B.1.640.1 and B.1.640.2 variants to interact with cellular components, such as cell surface receptors. Full article
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Article
A Retrospective Study of the Efficacy of Albendazole and Diethylcarbamazine for the Treatment of Human Toxocariasis
Pathogens 2022, 11(7), 813; https://doi.org/10.3390/pathogens11070813 - 20 Jul 2022
Viewed by 300
Abstract
In the Department of Parasitology and Mycology of Toulouse University Hospitals, patients presenting with common/covert toxocariasis were treated either with albendazole (39 cases) or with diethylcarbamazine (32 cases). Albendazole (ABZ) was given at 10 mg/kg b/w daily for 14 days, and diethylcarbamazine (DEC) [...] Read more.
In the Department of Parasitology and Mycology of Toulouse University Hospitals, patients presenting with common/covert toxocariasis were treated either with albendazole (39 cases) or with diethylcarbamazine (32 cases). Albendazole (ABZ) was given at 10 mg/kg b/w daily for 14 days, and diethylcarbamazine (DEC) was given at 4 mg/kg b/w daily for 21 days. In both groups, follow-up consultations occurred approximately 48 days after the end of the anthelmintic therapy. ABZ and DEC displayed a similar efficacy on the kinetics of the clinical picture (−64.5% of reduction vs. −72.7%, respectively) and on the levels of blood eosinophilia, serum eosinophil cationic protein and serum total IgE. However, the effect of the medication on the laboratory parameters was moderate. The rate of adverse reactions was similar in both groups (38% for ABZ vs. 31% for DEC), but DEC-treated patients complained of more intense and long-lasting side effects. The DEC group had more major adverse reactions, resulting in the termination of the anthelmintic treatment. The results from this retrospective study bring further arguments for considering ABZ, given at 10 mg/kg daily for 2 weeks, as the drug of choice in the treatment of human toxocariasis. Full article
(This article belongs to the Special Issue Bacterial, Fungal and Parasitic Zoonoses)
Article
Survival of Campylobacter jejuni Co-Cultured with Salmonella spp. in Aerobic Conditions
Pathogens 2022, 11(7), 812; https://doi.org/10.3390/pathogens11070812 - 20 Jul 2022
Viewed by 346
Abstract
Campylobacter and Salmonella are responsible for the two major foodborne zoonotic diseases in Europe; poultry is the main infection source. Campylobacter cannot grow under aerobic conditions, but can show aerobic survival when co-cultured with other microorganisms; however, its interaction with Salmonella has not [...] Read more.
Campylobacter and Salmonella are responsible for the two major foodborne zoonotic diseases in Europe; poultry is the main infection source. Campylobacter cannot grow under aerobic conditions, but can show aerobic survival when co-cultured with other microorganisms; however, its interaction with Salmonella has not been studied yet. In this study, these two bacteria were co-cultured under controlled aerobic conditions. Different concentrations and strains of C. jejuni were incubated with or without different Salmonella serotypes (10 CFU) at 37 °C for 16 h. C. jejuni did not grow after incubation with or without Salmonella. The survival of C. jejuni was observed only for the highest initial concentration of 6 log CFU/mL with or without Salmonella. However, its survival was significantly higher when co-cultured with Salmonella. No survival was observed at lower concentrations. C. jejuni survival was positively affected by the presence of Salmonella but depended on the Salmonella serotype, the C. jejuni strain and the initial concentration. On the other hand, the Salmonella enumerations were not affected by C. jejuni. Our results suggest potential interactions between Salmonella and C. jejuni that require further investigations for a clearer understanding of their behavior in natural habitats. Full article
(This article belongs to the Collection Campylobacter Infections Collection)
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Editorial
Advances in the Immunobiology of Parasitic Diseases
Pathogens 2022, 11(7), 811; https://doi.org/10.3390/pathogens11070811 - 20 Jul 2022
Viewed by 272
Abstract
Notwithstanding that most biomedical research today focuses on the pandemic caused by the SARs-CoV-2 virus, there are many unresolved diseases that are almost forgotten worldwide [...] Full article
(This article belongs to the Special Issue Advances in the Immunobiology of Parasitic Diseases)
Article
Assembly, Annotation, and Comparative Whole Genome Sequence of Fusarium verticillioides Isolated from Stored Maize Grains
Pathogens 2022, 11(7), 810; https://doi.org/10.3390/pathogens11070810 - 20 Jul 2022
Viewed by 341
Abstract
Fusarium verticillioides is a plant pathogenic fungus affecting a wide range of crops worldwide due to its toxigenic properties. F. verticillioides BIONCL4 strain was isolated from stored maize grain samples in India, and produces high amount of fumonisin B1 (FB1). We report a [...] Read more.
Fusarium verticillioides is a plant pathogenic fungus affecting a wide range of crops worldwide due to its toxigenic properties. F. verticillioides BIONCL4 strain was isolated from stored maize grain samples in India, and produces high amount of fumonisin B1 (FB1). We report a comparative genomic analysis of F. verticillioides, covering the basic genome information, secretome, and proteins involved in host–pathogen interactions and mycotoxin biosynthesis. Whole-genome sequencing (WGS) was performed using the Illumina platform with an assembly size of 42.91 Mb, GC content of 48.24%, and 98.50% coverage with the reference genome (GCA000149555). It encodes 15,053 proteins, including 2058 secretory proteins, 676 classical secretory proteins, and 569 virulence and pathogenicity-related proteins. There were also 1447 genes linked to carbohydrate active enzymes (CaZymes) and 167 genes related to mycotoxin production. Furthermore, F. verticillioides genome comparison revealed information about the species’ evolutionary history. The overall study helps in disease prevention and management of mycotoxins to ensure food safety. Full article
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Review
Role of Microglia in Herpesvirus-Related Neuroinflammation and Neurodegeneration
Pathogens 2022, 11(7), 809; https://doi.org/10.3390/pathogens11070809 - 19 Jul 2022
Viewed by 363
Abstract
Neuroinflammation is defined as an inflammatory state within the central nervous system (CNS). Microglia conprise the resident tissue macrophages of the neuronal tissue. Upon viral infection of the CNS, microglia become activated and start to produce inflammatory mediators important for clearance of the [...] Read more.
Neuroinflammation is defined as an inflammatory state within the central nervous system (CNS). Microglia conprise the resident tissue macrophages of the neuronal tissue. Upon viral infection of the CNS, microglia become activated and start to produce inflammatory mediators important for clearance of the virus, but an excessive neuroinflammation can harm nearby neuronal cells. Herpesviruses express several molecular mechanisms, which can modulate apoptosis of infected neurons, astrocytes and microglia but also divert immune response initiated by the infected cells. In this review we also describe the link between virus-related neuroinflammation, and development of neurodegenerative diseases. Full article
(This article belongs to the Special Issue Modification of Cellular Response by HSV)
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Article
Molecular Epidemiology and Baseline Resistance of Hepatitis C Virus to Direct Acting Antivirals in Croatia
Pathogens 2022, 11(7), 808; https://doi.org/10.3390/pathogens11070808 - 19 Jul 2022
Viewed by 313
Abstract
Molecular epidemiology of hepatitis C virus (HCV) is exceptionally complex due to the highly diverse HCV genome. Genetic diversity, transmission dynamics, and epidemic history of the most common HCV genotypes were inferred by population sequencing of the HCV NS3, NS5A, and NS5B region [...] Read more.
Molecular epidemiology of hepatitis C virus (HCV) is exceptionally complex due to the highly diverse HCV genome. Genetic diversity, transmission dynamics, and epidemic history of the most common HCV genotypes were inferred by population sequencing of the HCV NS3, NS5A, and NS5B region followed by phylogenetic and phylodynamic analysis. The results of this research suggest high overall prevalence of baseline NS3 resistance associate substitutions (RAS) (33.0%), moderate prevalence of NS5A RAS (13.7%), and low prevalence of nucleoside inhibitor NS5B RAS (8.3%). Prevalence of RAS significantly differed according to HCV genotype, with the highest prevalence of baseline resistance to NS3 inhibitors and NS5A inhibitors observed in HCV subtype 1a (68.8%) and subtype 1b (21.3%), respectively. Phylogenetic tree reconstructions showed two distinct clades within the subtype 1a, clade I (62.4%) and clade II (37.6%). NS3 RAS were preferentially associated with clade I. Phylogenetic analysis demonstrated that 27 (9.0%) HCV sequences had a presumed epidemiological link with another sequence and classified into 13 transmission pairs or clusters which were predominantly comprised of subtype 3a viruses and commonly detected among intravenous drug users (IDU). Phylodynamic analyses highlighted an exponential increase in subtype 1a and 3a effective population size in the late 20th century, which is a period associated with an explosive increase in the number of IDU in Croatia. Full article
(This article belongs to the Special Issue Molecular Diagnostic and Epidemiology of Viral Infections)
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Article
Disturbance Ecology Meets Bovine Tuberculosis (bTB) Epidemiology: A Before-and-After Study on the Association between Forest Clearfelling and bTB Herd Risk in Cattle Herds
Pathogens 2022, 11(7), 807; https://doi.org/10.3390/pathogens11070807 - 19 Jul 2022
Viewed by 349
Abstract
Disturbance ecology refers to the study of discrete processes that disrupt the structure or dynamics of an ecosystem. Such processes can, therefore, affect wildlife species ecology, including those that are important pathogen hosts. We report on an observational before-and-after study on the association [...] Read more.
Disturbance ecology refers to the study of discrete processes that disrupt the structure or dynamics of an ecosystem. Such processes can, therefore, affect wildlife species ecology, including those that are important pathogen hosts. We report on an observational before-and-after study on the association between forest clearfelling and bovine tuberculosis (bTB) herd risk in cattle herds, an episystem where badgers (Meles meles) are the primary wildlife spillover host. The study design compared herd bTB breakdown risk for a period of 1 year prior to and after exposure to clearfelling across Ireland at sites cut in 2015–2017. The percent of herds positive rose from 3.47% prior to clearfelling to 4.08% after exposure. After controlling for confounders (e.g., herd size, herd type), we found that cattle herds significantly increased their odds of experiencing a bTB breakdown by 1.2-times (95%CIs: 1.07–1.36) up to 1 year after a clearfell risk period. Disturbance ecology of wildlife reservoirs is an understudied area with regards to shared endemic pathogens. Epidemiological observational studies are the first step in building an evidence base to assess the impact of such disturbance events; however, such studies are limited in inferring the mechanism for any changes in risk observed. The current cohort study suggested an association between clearfelling and bTB risk, which we speculate could relate to wildlife disturbance affecting pathogen spillback to cattle, though the study design precludes causal inference. Further studies are required. However, ultimately, integration of epidemiology with wildlife ecology will be important for understanding the underlying mechanisms involved, and to derive suitable effective management proposals, if required. Full article
(This article belongs to the Section Bacterial Pathogens)
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Article
GMP Manufacturing and IND-Enabling Studies of a Recombinant Hyperimmune Globulin Targeting SARS-CoV-2
Pathogens 2022, 11(7), 806; https://doi.org/10.3390/pathogens11070806 - 19 Jul 2022
Viewed by 471
Abstract
Conventionally, hyperimmune globulin drugs manufactured from pooled immunoglobulins from vaccinated or convalescent donors have been used in treating infections where no treatment is available. This is especially important where multi-epitope neutralization is required to prevent the development of immune-evading viral mutants that can [...] Read more.
Conventionally, hyperimmune globulin drugs manufactured from pooled immunoglobulins from vaccinated or convalescent donors have been used in treating infections where no treatment is available. This is especially important where multi-epitope neutralization is required to prevent the development of immune-evading viral mutants that can emerge upon treatment with monoclonal antibodies. Using microfluidics, flow sorting, and a targeted integration cell line, a first-in-class recombinant hyperimmune globulin therapeutic against SARS-CoV-2 (GIGA-2050) was generated. Using processes similar to conventional monoclonal antibody manufacturing, GIGA-2050, comprising 12,500 antibodies, was scaled-up for clinical manufacturing and multiple development/tox lots were assessed for consistency. Antibody sequence diversity, cell growth, productivity, and product quality were assessed across different manufacturing sites and production scales. GIGA-2050 was purified and tested for good laboratory procedures (GLP) toxicology, pharmacokinetics, and in vivo efficacy against natural SARS-CoV-2 infection in mice. The GIGA-2050 master cell bank was highly stable, producing material at consistent yield and product quality up to >70 generations. Good manufacturing practices (GMP) and development batches of GIGA-2050 showed consistent product quality, impurity clearance, potency, and protection in an in vivo efficacy model. Nonhuman primate toxicology and pharmacokinetics studies suggest that GIGA-2050 is safe and has a half-life similar to other recombinant human IgG1 antibodies. These results supported a successful investigational new drug application for GIGA-2050. This study demonstrates that a new class of drugs, recombinant hyperimmune globulins, can be manufactured consistently at the clinical scale and presents a new approach to treating infectious diseases that targets multiple epitopes of a virus. Full article
(This article belongs to the Collection SARS-CoV-2 Infection and COVID-19 Disease)
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Article
Preparation and Storage of Cryoprecipitate Derived from Amotosalen and UVA-Treated Apheresis Plasma and Assessment of In Vitro Quality Parameters
Pathogens 2022, 11(7), 805; https://doi.org/10.3390/pathogens11070805 - 18 Jul 2022
Viewed by 286
Abstract
Cryoprecipitate is a plasma-derived blood product, enriched for fibrinogen, factor VIII, factor XIII, and von Willebrand factor. Due to infectious risk, the use of cryoprecipitate in Central Europe diminished over the last decades. However, after the introduction of various pathogen-reduction technologies for plasma, [...] Read more.
Cryoprecipitate is a plasma-derived blood product, enriched for fibrinogen, factor VIII, factor XIII, and von Willebrand factor. Due to infectious risk, the use of cryoprecipitate in Central Europe diminished over the last decades. However, after the introduction of various pathogen-reduction technologies for plasma, cryoprecipitate production in blood centers is a feasible alternative to pharmaceutical fibrinogen concentrate with a high safety profile. In our study, we evaluated the feasibility of the production of twenty-four cryoprecipitate units from pools of two units of apheresis plasma pathogen reduced using amotosalen and ultraviolet light A (UVA) (INTERCEPT® Blood System). The aim was to assess the compliance of the pathogen-reduced cryoprecipitate with the European Directorate for the Quality of Medicines (EDQM) guidelines and the stability of coagulation factors after frozen (≤−25 °C) storage and five-day liquid storage at ambient temperature post-thawing. All pathogen-reduced cryoprecipitate units fulfilled the European requirements for fibrinogen, factor VIII and von Willebrand factor content post-preparation. After five days of liquid storage, content of these factors exceeded the minimum values in the European requirements and the content of other factors was sufficient. Our method of production of cryoprecipitate using pathogen-reduced apheresis plasma in a jumbo bag is feasible and efficient. Full article
(This article belongs to the Special Issue Pathogen Reduction of Blood Bank Components)
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Brief Report
Improving Drug Sensitivity of HIV-1 Protease Inhibitors by Restriction of Cellular Efflux System in a Fission Yeast Model
Pathogens 2022, 11(7), 804; https://doi.org/10.3390/pathogens11070804 - 16 Jul 2022
Viewed by 381
Abstract
Fission yeast can be used as a cell-based system for high-throughput drug screening. However, higher drug concentrations are often needed to achieve the same effect as in mammalian cells. Our goal here was to improve drug sensitivity so reduced drugs could be used. [...] Read more.
Fission yeast can be used as a cell-based system for high-throughput drug screening. However, higher drug concentrations are often needed to achieve the same effect as in mammalian cells. Our goal here was to improve drug sensitivity so reduced drugs could be used. Three different methods affecting drug uptakes were tested using an FDA-approved HIV-1 protease inhibitor (PI) drug Darunavir (DRV). First, we tested whether spheroplasts without cell walls increase the drug sensitivity. Second, we examined whether electroporation could be used. Although small improvements were observed, neither of these two methods showed significant increase in the EC50 values of DRV compared with the traditional method. In contrast, when DRV was tested in a mutant strain PR836 that lacks key proteins regulating cellular efflux, a significant increase in the EC50 was observed. A comparison of nine FDA-approved HIV-1 PI drugs between the wild-type RE294 strain and the mutant PR836 strain showed marked enhancement of the drug sensitivities ranging from an increase of 0.56 log to 2.48 logs. Therefore, restricting cellular efflux through the adaption of the described fission yeast mutant strain enhances the drug sensitivity, reduces the amount of drug used, and increases the chance of success in future drug discovery. Full article
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Article
Establishing a Herpesvirus Quiescent Infection in Differentiated Human Dorsal Root Ganglion Neuronal Cell Line Mediated by Micro-RNA Overexpression
Pathogens 2022, 11(7), 803; https://doi.org/10.3390/pathogens11070803 - 16 Jul 2022
Viewed by 330
Abstract
HSV-1 is a neurotropic pathogen associated with severe encephalitis, excruciating orofacial sensation, and other chronic neuropathic complications. After the acute infection, the virus may establish a lifelong latency in the neurons of trigeminal ganglia (TG) and other sensory and autonomic ganglia, including the [...] Read more.
HSV-1 is a neurotropic pathogen associated with severe encephalitis, excruciating orofacial sensation, and other chronic neuropathic complications. After the acute infection, the virus may establish a lifelong latency in the neurons of trigeminal ganglia (TG) and other sensory and autonomic ganglia, including the dorsal root ganglia (DRG), etc. The reactivation occurred periodically by a variety of physical or emotional stressors. We have been developing a human DRG neuronal cell-culture model HD10.6, which mimics the mature neurons for latency and reactivation with robust neuronal physiology. We found that miR124 overexpression without acyclovir (ACV) could maintain the virus in a quiescent infection, with the accumulation of latency-associate transcript (LAT). The immediate-early (IE) gene ICP0, on the other hand, was very low and the latent viruses could be reactivated by trichostatin A (TSA) treatment. Together, these observations suggested a putative role of microRNA in promoting HSV-1 latency in human neurons. Full article
(This article belongs to the Special Issue Host–Virus Interactions in the Nervous System)
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Article
Anthroponotic-Based Transfer of Staphylococcus to Dog: A Case Study
Pathogens 2022, 11(7), 802; https://doi.org/10.3390/pathogens11070802 - 15 Jul 2022
Viewed by 351
Abstract
Although usually harmless, Staphylococcus spp. can cause nosocomial and community-onset skin and soft tissue infections in both humans and animals; thus, it is considered a significant burden for healthcare systems worldwide. Companion animals have been identified as potential reservoirs of pathogenic Staphylococcus with [...] Read more.
Although usually harmless, Staphylococcus spp. can cause nosocomial and community-onset skin and soft tissue infections in both humans and animals; thus, it is considered a significant burden for healthcare systems worldwide. Companion animals have been identified as potential reservoirs of pathogenic Staphylococcus with specific reference to Methicillin Resistant Staphylococcus aureus (MRSA). In this study, we investigated the circulation and the genetic relationships of a collection of Staphylococcus spp. isolates in a family composed of four adults (a mother, father, grandmother, and grandfather), one child, and a dog, which were sampled over three years. The routes of transmission among humans and between humans and the dog werelyzed. The results displayed the circulation of many Staphylococcus lineages, belonging to different species and sequence types (ST) and being related to both human and pet origins. However, among the observed host-switch events, one of them clearly underpinnthroponotic route from a human to a dog. This suggests that companion animals can potentially have a role as a carrier of Staphylococcus, thus posing a serious concern about MRSA spreading within human and animal microbial communities. Full article
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Article
Complete Genomes of Theileria orientalis Chitose and Buffeli Genotypes Reveal within Species Translocations and Differences in ABC Transporter Content
Pathogens 2022, 11(7), 801; https://doi.org/10.3390/pathogens11070801 - 15 Jul 2022
Viewed by 323
Abstract
Theileria orientalis causes losses to cattle producers in Eastern Asia, Oceania and, more recently, North America. One pathogenic genotype (Ikeda) has been sequenced to the chromosomal level, while only draft genomes exist for globally distributed Chitose and Buffeli genotypes. To provide an accurate [...] Read more.
Theileria orientalis causes losses to cattle producers in Eastern Asia, Oceania and, more recently, North America. One pathogenic genotype (Ikeda) has been sequenced to the chromosomal level, while only draft genomes exist for globally distributed Chitose and Buffeli genotypes. To provide an accurate comparative gene-level analysis and help further understand their pathogenicity, we sequenced isolates of the Chitose and Buffeli genotypes of T. orientalis using long-read sequencing technology. A combination of several long-read assembly methods and short reads produced chromosomal-level assemblies for both Fish Creek (Chitose) and Goon Nure (Buffeli) isolates, including the first complete and circular apicoplast genomes generated for T. orientalis. Comparison with the Shintoku (Ikeda) reference sequence showed both large and small translocations in T. orientalis Buffeli, between chromosomes 2 and 3 and chromosomes 1 and 4, respectively. Ortholog clustering showed expansion of ABC transporter genes in Chitose and Buffeli. However, differences in several genes of unknown function, including DUF529/FAINT-domain-containing proteins, were also identified and these genes were more prevalent in Ikeda and Chitose genotypes. Phylogenetics and similarity measures were consistent with previous short-read genomic analysis. The generation of chromosomal sequences for these highly prevalent T. orientalis genotypes will also support future studies of population genetics and mixed genotype infections. Full article
(This article belongs to the Special Issue Bovine Theileriosis Caused by the Theileria orientalis Group)
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Review
RNA Viruses, Pregnancy and Vaccination: Emerging Lessons from COVID-19 and Ebola Virus Disease
Pathogens 2022, 11(7), 800; https://doi.org/10.3390/pathogens11070800 - 15 Jul 2022
Viewed by 587
Abstract
Pathogenic viruses with an RNA genome represent a challenge for global human health since they have the tremendous potential to develop into devastating pandemics/epidemics. The management of the recent COVID-19 pandemic was possible to a certain extent only because of the strong foundations [...] Read more.
Pathogenic viruses with an RNA genome represent a challenge for global human health since they have the tremendous potential to develop into devastating pandemics/epidemics. The management of the recent COVID-19 pandemic was possible to a certain extent only because of the strong foundations laid by the research on previous viral outbreaks, especially Ebola Virus Disease (EVD). A clear understanding of the mechanisms of the host immune response generated upon viral infections is a prime requisite for the development of new therapeutic strategies. Hence, we present here a comparative study of alterations in immune response upon SARS-CoV-2 and Ebola virus infections that illustrate many common features. Vaccination and pregnancy are two important aspects that need to be studied from an immunological perspective. So, we summarize the outcomes and immune responses in vaccinated and pregnant individuals in the context of COVID-19 and EVD. Considering the significance of immunomodulatory approaches in combating both these diseases, we have also presented the state of the art of such therapeutics and prophylactics. Currently, several vaccines against these viruses have been approved or are under clinical trials in various parts of the world. Therefore, we also recapitulate the latest developments in these which would inspire researchers to look for possibilities of developing vaccines against many other RNA viruses. We hope that the similar aspects in COVID-19 and EVD open up new avenues for the development of pan-viral therapies. Full article
(This article belongs to the Special Issue Host Immune Responses to RNA Viruses)
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Article
Productive Replication of HIV-1 but Not SIVmac in Small Ruminant Cells
Pathogens 2022, 11(7), 799; https://doi.org/10.3390/pathogens11070799 - 15 Jul 2022
Viewed by 486
Abstract
Animal lentiviruses (LVs) have been proven to have the capacity to cross the species barrier, to adapt in the new hosts, and to increase their pathogenesis, therefore leading to the emergence of threatening diseases. However, their potential for widespread diffusion is limited by [...] Read more.
Animal lentiviruses (LVs) have been proven to have the capacity to cross the species barrier, to adapt in the new hosts, and to increase their pathogenesis, therefore leading to the emergence of threatening diseases. However, their potential for widespread diffusion is limited by restrictive cellular factors that block viral replication in the cells of many species. In previous studies, we demonstrated that the restriction of CAEV infection of sheep choroid plexus cells was due to aberrant post-translation cleavage of the CAEV Env gp170 precursor. Later, we showed that the lack of specific receptor(s) for caprine encephalitis arthritis virus (CAEV) on the surface of human cells was the only barrier to their infection. Here, we examined whether small ruminant (SR) cells can support the replication of primate LVs. Three sheep and goat cell lines were inoculated with cell-free HIV-1 and SIVmac viral stocks or transfected with infectious molecular clone DNAs of these viruses. The two recombinant lentiviral clones contained the green fluorescent protein (GFP) reporter sequence. Infection was detected by GFP expression in target cells, and the infectious virus produced and released in the culture medium of treated cells was detected using the indicator TZM-bl cell line. Pseudotyped HIV-GFP and SIV-GFP with vesicular stomatitis virus G glycoprotein (VSV-G) allowed the cell receptors to be overcome for virus entry to further evaluate the viral replication/restriction in SR cells. As expected, neither HIV nor SIV viruses infected any of the SR cells. In contrast, the transfection of plasmid DNAs of the infectious molecular clones of both viruses in SR cells produced high titers of infectious viruses for human indicators, but not SR cell lines. Surprisingly, SR cells inoculated with HIV-GFP/VSV-G, but not SIV-GFP/VSV-G, expressed the GFP and produced a virus that efficiently infected the human indictor, but not the SR cells. Collectively, these data provide a demonstration of the lack of replication of the SIVmac genome in SR cells, while, in contrast, there was no restriction on the replication of the IV-1 genome in these cells. However, because of the lack of functional receptors to SIVmac and HIV-1 at the surface of SR cells, there is specific lentiviral entry. Full article
(This article belongs to the Special Issue Animal Retrovirus)
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Article
Ginger Is a Potential Therapeutic for Chronic Toxoplasmosis
Pathogens 2022, 11(7), 798; https://doi.org/10.3390/pathogens11070798 - 15 Jul 2022
Viewed by 438
Abstract
Background:Toxoplasma gondii (T. gondii) is an opportunistic parasite that causes serious diseases in humans, particularly immunocompromised individuals and pregnant women. To date, there are limited numbers of therapeutics for chronic toxoplasmosis which necessitate the discovery of effective and safe therapeutics. [...] Read more.
Background:Toxoplasma gondii (T. gondii) is an opportunistic parasite that causes serious diseases in humans, particularly immunocompromised individuals and pregnant women. To date, there are limited numbers of therapeutics for chronic toxoplasmosis which necessitate the discovery of effective and safe therapeutics. In the present study, we aimed to evaluate the antitoxoplasmosis potential of ginger extract in mice with experimentally induced chronic toxoplasmosis. Results: Treatment with ginger extract significantly reduced cysts count in the brains of T. gondii-infected mice with a marked alleviation of edema and inflammation, and a reversal of neuronal injury. Moreover, ginger extract treatment reduced inflammation in liver and lungs and protected hepatocytes from infection-induced degeneration. Consistently, apoptosis was significantly mitigated in the brains of ginger extract-treated mice compared to infected untreated animals or spiramycin-treated animals. Methods: Four groups of Swiss albino mice (10 mice each) were used. The first group was not infected, whereas 3 groups were infected with Me49 T. gondii strains. One infected group remained untreated (infected untreated), whereas the other two infected groups were treated with either ginger extract (250 mg/kg) or spiramycin (positive control; 100 mg/kg), respectively. The therapeutic potential of ginger extract was evaluated by calculation of the parasite burden in infected animals, and examination of the infected tissues for reduced pathologic changes. Conclusions: Our results showed for the first time that ginger extract exhibited marked therapeutic effects in mice with chronic T. gondii infection which indicates that it can be used as a safe and effective treatment for chronic toxoplasmosis. Full article
(This article belongs to the Special Issue Optimizing Treatment for Parasitic Infections)
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Communication
First Report of a Complete Genome Sequence of a Variant African Swine Fever Virus in the Mekong Delta, Vietnam
Pathogens 2022, 11(7), 797; https://doi.org/10.3390/pathogens11070797 - 15 Jul 2022
Viewed by 416
Abstract
The objective of this study is to report the complete-genome sequence of a field African swine fever (ASF) virus (ASFV), namely ASF/VN/CanTho-OM/2021, which caused a fatal outbreak in domestic pigs in the Mekong Delta. Complete-genome sequencing detected an 18 bp nucleotide deletion in [...] Read more.
The objective of this study is to report the complete-genome sequence of a field African swine fever (ASF) virus (ASFV), namely ASF/VN/CanTho-OM/2021, which caused a fatal outbreak in domestic pigs in the Mekong Delta. Complete-genome sequencing detected an 18 bp nucleotide deletion in the EP402R gene (encoding for serotype-specific proteins CD2v) of ASF/VN/CanTho-OM/2021, which was determined to belong to genotype 2 and serotype 8. This mutation pattern was confirmed as unique in GenBank; thus, ASF/VN/CanTho-OM/2021 can be considered a novel variant, with a potential change of sero-characteristics within genotype 2. An additional unique mutation of 78 bp nucleotide insertion was also observed in the B475L gene. Additionally, four copies of tandem repeat sequences were found in the intergenic region (IGR) located between I73R and I329L, previously assigned as the IGR III variant. This study is the first to report the complete genome of ASFV in the Mekong Delta, and it highlights the necessity of strengthening molecular surveillance to provide further knowledge on the evolution and incursion of ASFV in the Mekong Delta and Vietnam. Full article
(This article belongs to the Collection Emerging and Re-emerging Pathogens)
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Review
Gut Microbes and Neuropathology: Is There a Causal Nexus?
Pathogens 2022, 11(7), 796; https://doi.org/10.3390/pathogens11070796 - 14 Jul 2022
Viewed by 574
Abstract
The gut microbiota is a virtual organ which produces a myriad of molecules that the brain and other organs require. Humans and microbes are in a symbiotic relationship, we feed the microbes, and in turn, they provide us with essential molecules. Bacteroidetes and [...] Read more.
The gut microbiota is a virtual organ which produces a myriad of molecules that the brain and other organs require. Humans and microbes are in a symbiotic relationship, we feed the microbes, and in turn, they provide us with essential molecules. Bacteroidetes and Firmicutes phyla account for around 80% of the total human gut microbiota, and approximately 1000 species of bacteria have been identified in the human gut. In adults, the main factors influencing microbiota structure are diet, exercise, stress, disease and medications. In this narrative review, we explore the involvement of the gut microbiota in Parkinson’s disease, Alzheimer’s disease, multiple sclerosis and autism, as these are such high-prevalence disorders. We focus on preclinical studies that increase the understanding of disease pathophysiology. We examine the potential for targeting the gut microbiota in the development of novel therapies and the limitations of the currently published clinical studies. We conclude that while the field shows enormous promise, further large-scale studies are required if a causal link between these disorders and gut microbes is to be definitively established. Full article
(This article belongs to the Collection Current Status of Research on Gut Metabolites and Microbiota)
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Article
Pathogenicity and Metabolites of Purpureocillium lavendulum YMF1.00683 against Meloidogyne incognita
Pathogens 2022, 11(7), 795; https://doi.org/10.3390/pathogens11070795 - 14 Jul 2022
Viewed by 299
Abstract
Purpureocillium lavendulum is a biological control agent with several registered products that can parasitize the eggs and larvae of various pathogenic nematodes. In this study, the pathogenicity and secondary metabolites of the fungus P. lavendulum YMF1.00683 were investigated. The strain YMF1.00683 had infection [...] Read more.
Purpureocillium lavendulum is a biological control agent with several registered products that can parasitize the eggs and larvae of various pathogenic nematodes. In this study, the pathogenicity and secondary metabolites of the fungus P. lavendulum YMF1.00683 were investigated. The strain YMF1.00683 had infection efficiency against the plant root-knot nematode Meloidogyne incognita. The strain’s process of infecting nematodes was observed under a microscope. Moreover, seven metabolites, including a new sterol (1), were isolated and identified from cultures of YMF1.0068 in Sabouraud’s dextrose agar. A bioassay showed that 5-methoxymethyl-1H-pyrrole-2-carboxaldehyde (7) is toxic to M. incognita and affects the egg hatching. It caused 98.23% mortality in M. incognita and could inhibit 80.78% of the hatching eggs at 400 μg/mL over a period of 96 h. Furthermore, 5-methoxymethyl-1H-pyrrole-2-carboxaldehyde (7) showed a strong avoidance effect at 40 ppm, and its chemotactic index value was −0.37. The results indicate that P. lavendulum could produce active metabolites against M. incognita. Full article
(This article belongs to the Special Issue Microbe-Nematode Interactions)
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Article
Characterization of Bordetella pertussis Strains Isolated from India
Pathogens 2022, 11(7), 794; https://doi.org/10.3390/pathogens11070794 - 14 Jul 2022
Viewed by 340
Abstract
Despite high level vaccination and the availability of two different types of vaccines, whole cell (wP) and acellular vaccines (aP), the resurgence of pertussis has been reported in many countries. Antigenic variation within circulating and vaccine strains is the most documented reason reported [...] Read more.
Despite high level vaccination and the availability of two different types of vaccines, whole cell (wP) and acellular vaccines (aP), the resurgence of pertussis has been reported in many countries. Antigenic variation within circulating and vaccine strains is the most documented reason reported for the resurgence of pertussis. Research on genetic divergence among circulating and vaccine strains has largely been reported in countries using aP vaccines. There are inadequate data available for antigenic variation in B. pertussis from wP-using countries. India has used wP for more than 40 years in their primary immunization program. The present study reports five clinical isolates of B. pertussis from samples of pediatric patients with pertussis symptoms observed in India. Genotypic and phenotypic characterization of clinical isolates were performed by serotyping, genotyping, whole genome analyses and comparative genomics. All clinical isolates showed serotype 1, 2 and 3 based on the presence of fimbriae 2 and 3. Genotyping showed genetic similarities in allele types for five aP genes within vaccine strains and clinical isolates reported from India. The presence of the ptxP3 genotype was observed in two out of five clinical isolates. Whole-genome sequencing was performed for clinical isolates using the hybrid strategy of combining Illumina (short reads) and oxford nanopore (long reads) sequencing strategies. Clinical isolates (n = 5) and vaccine strains (n = 7) genomes of B. pertussis from India were compared with 744 B. pertussis closed genomes available in the public databases. The phylogenomic comparison of B. pertussis genomes reported from India will be advantageous in better understanding pertussis resurgence reported globally with respect to pathogen adaptation. Full article
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Article
Evolution of the Clinical Profile and Outcomes of Unvaccinated Patients Affected by Critical COVID-19 Pneumonia from the Pre-Vaccination to the Post-Vaccination Waves in Italy
Pathogens 2022, 11(7), 793; https://doi.org/10.3390/pathogens11070793 - 14 Jul 2022
Viewed by 346
Abstract
The vaccination campaign and the new SARS-CoV-2 variants may have changed the clinical profile and outcomes of patients admitted to sub-intensive unit care. We conducted a retrospective study aimed to compare the clinical and radiological features of unvaccinated critical COVID-19 patients hospitalized during [...] Read more.
The vaccination campaign and the new SARS-CoV-2 variants may have changed the clinical profile and outcomes of patients admitted to sub-intensive unit care. We conducted a retrospective study aimed to compare the clinical and radiological features of unvaccinated critical COVID-19 patients hospitalized during the last pandemic wave (December 2021–February 2022, No-Vax group) and before starting the vaccination campaign (March–December 2020, Pre-Vax group). The No-Vax group was also compared with vaccinated patients of the same pandemic wave (Vax group). With respect to the Pre-Vax group, the No-Vax group contained a higher percentage of smokers (p = 0.0007) and a lower prevalence of males (p = 0.0003). At admission, the No-Vax patients showed both a higher CT score of pneumonia and a worse severe respiratory failure (p < 0.0001). In the No-Vax group, a higher percentage of deaths occurred, though this was not significant. In comparison with the No-Vax group, the Vax patients were older (p = 0.0097), with a higher Charlson comorbidity index (p < 0.0001) and a significantly lower HRCT score (p = 0.0015). The percentage of deaths was not different between the two groups. The No-Vax patients showed a more severe disease in comparison with the Pre-Vax patients, and were younger and had fewer comorbidities than the Vax patients. Full article
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Review
Gurltia paralysans: A Neglected Angio-Neurotropic Parasite of Domestic Cats (Felis catus) and Free-Ranging Wild Felids (Leopardus spp.) in South America
Pathogens 2022, 11(7), 792; https://doi.org/10.3390/pathogens11070792 - 13 Jul 2022
Viewed by 327
Abstract
Gurltia paralysans is a neglected and re-emerging metastrongyloid angio-neurotropic nematode causing severe chronic meningomyelitis in domestic cats (Felis catus) as well as in free-ranging small wild felids such as kodkods (Leopardus guigna), margays (Leopardus wiedii) and the [...] Read more.
Gurltia paralysans is a neglected and re-emerging metastrongyloid angio-neurotropic nematode causing severe chronic meningomyelitis in domestic cats (Felis catus) as well as in free-ranging small wild felids such as kodkods (Leopardus guigna), margays (Leopardus wiedii) and the northern tiger cat (Leopardus triginus) in South America. Within these definitive hosts (DH), adult males and females of G. paralysans parasitize the leptomeningeal veins of the subarachnoid space and/or the meningeal veins of spinal cord parenchyma, inducing vascular alterations. Feline gurltiosis has been associated with progressive thrombophlebitis of the meningeal veins, resulting in ambulatory paraparesis, paraplegia, ataxia, hindlimb proprioceptive deficit, uni- or bilateral hyperactive patellar reflexes, faecal and urinary incontinence, and tail paralysis. The complete life cycle of G. paralysans has not been elucidated yet, but most probably involves gastropods as obligate intermediate hosts (IH). In terms of epidemiology, G. paralysans infections in domestic and wild felids are scattered around various South American countries, with hyperendemic areas in southern parts of Chile. Etiological diagnosis of G. paralysans still represents a challenge for clinicians due to a lack of evidence of the excretion of either eggs or larvae in faeces or in other body fluids. Diagnosis is based on clinical neurological signs, imaging findings through computed tomography (CT), myelography, magnetic resonance imaging (MRI), and post mortem examination. Nonetheless, novel diagnostic tools have been developed, including semi-nested PCR for detecting circulating G. paralysans DNA in the cerebrospinal fluid, serum and blood samples as well as in serological diagnostic kits detecting parasite-derived antigens, but these need validation for routine usage. The hypothetical life cycle of G. paralysans is addressed in this article, including the exogenous stages (i.e., eggs, and first- (L1), second- (L2) and third-stage (L3) larvae) and obligate gastropod IH and/or paratenic hosts (PH), and we propose possible anatomical migration routes of infective L3 that reach the leptomeningeal veins in vivo. Finally, the pro-inflammatory endothelium- and leukocyte-derived innate immune reactions of the host against G. paralysans, which most likely result in thrombophlebitis and meningomyelitis, are briefly touched on. Full article
(This article belongs to the Section Parasitic Pathogens)
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Article
The Efficiency of Commercial Immunodiagnostic Assays for the Field Detection of Schistosoma japonicum Human Infections: A Meta-Analysis
Pathogens 2022, 11(7), 791; https://doi.org/10.3390/pathogens11070791 - 13 Jul 2022
Viewed by 294
Abstract
Although great strides have been achieved, schistosomiasis japonica remains a major public health concern in China. Immunodiagnostics have been widely accepted as the first choice in large-scale screening of Schistosoma japonicum human infections, and indirect hemagglutination test (IHA), enzyme-linked immunosorbent assay (ELISA), and [...] Read more.
Although great strides have been achieved, schistosomiasis japonica remains a major public health concern in China. Immunodiagnostics have been widely accepted as the first choice in large-scale screening of Schistosoma japonicum human infections, and indirect hemagglutination test (IHA), enzyme-linked immunosorbent assay (ELISA), and dipstick dye immunoassay (DDIA) are currently the three most common immunological tests for the diagnosis of S. japonicum human infections in China. This meta-analysis aimed to comprehensively assess the performance of IHA, ELISA, and DDIA for the field diagnosis of S. japonicum human infections. A total of 37 eligible publications were enrolled in the final analysis, including 29 Chinese publications and 8 English publications. No significant heterogeneities were detected among the studies reporting ELISA (I2 = 88%, p < 0.05), IHA (I2 = 95%, p < 0.05), or DDIA (I2 = 84%, p < 0.05). DDIA showed the highest pooled sensitivity (90.8%, 95% CI: 84.6% to 94.7%) and IHA presented the highest pooled specificity for detection of S. japonicum human infections (71.6%, 95% CI: 65.9% to 76.7%). Summary receiver operating characteristic (SROC) curve analysis showed that IHA exhibited the highest area under the SROC curve (AUC) (0.88, 95% CI: 0.85 to 0.9), and ELISA presented the lowest AUC (0.85, 95% CI: 0.82 to 0.88). Deeks’ funnel plots indicated no publication bias. IHA presented the highest sensitivity in medium-endemicity regions and the highest specificity for diagnosis of S. japonicum human infections in low-endemicity regions, and ELISA showed the highest diagnostic sensitivity in high-endemicity regions and the highest specificity in medium-endemicity regions, while DDIA exhibited the highest diagnostic sensitivity in high-endemicity regions and the highest specificity in low-endemicity regions. IHA and DDIA presented a higher efficiency for the diagnosis of S. japonicum human infections in marshland and lake regions than in hilly and mountainous regions, while ELISA showed a comparable diagnostic sensitivity between in marshland and lake regions and hilly and mountainous regions (88.3% vs. 88.6%), and a higher specificity in marshland and lake regions than in hilly and mountainous regions (60% vs. 48%). Our meta-analysis demonstrates a comparable diagnostic accuracy of IHA, ELISA, and DDIA for S. japonicum human infections, and the diagnostic sensitivity and specificity of IHA, ELISA, and DDIA vary in types and infection prevalence of endemic regions. DDIA combined with IHA is recommended as a tool for screening chemotherapy targets and seroepidemiological surveys during the stage moving towards schistosomiasis elimination in China. Further studies to examine the effectiveness of combinations of two or three immunological tests for diagnosis of S. japonicum human infections are warranted. Full article
(This article belongs to the Special Issue Advanced Diagnosis of Schistosomiasis)
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