Pathogens

14 pages, 3902 KiB

Open AccessEditor’s ChoiceArticle

Evaluation of Four Humanized NOD-Derived Mouse Models for Dengue Virus-2 Infection

by Hernando Gutierrez-Barbosa, Sandra Medina-Moreno, Federico Perdomo-Celis, Harry Davis, Joel V. Chua and Juan C. Zapata

Pathogens 2024, 13(8), 639; https://doi.org/10.3390/pathogens13080639 - 30 Jul 2024

Cited by 1 | Viewed by 1779

Abstract

Dengue is a significant public health problem with no specific viral treatment. One of the main challenges in studying dengue is the lack of adequate animal models recapitulating human immune responses. Most studies on humanized mice use NOD-scid IL2R gamma null (NSG) mice, [...] Read more.

Dengue is a significant public health problem with no specific viral treatment. One of the main challenges in studying dengue is the lack of adequate animal models recapitulating human immune responses. Most studies on humanized mice use NOD-scid IL2R gamma null (NSG) mice, which exhibit poor hematopoiesis for some cell populations. This study compares three humanized (hu) NOD-derived mouse models for dengue virus-2 (DENV-2) infection in the context of human cytokine expression. Three mouse strains (hu-NSG, hu-EXL, and hu-SGM3) received xenotransplants of human CD34+ fetal cord blood cells from a single donor, and one mouse strain received human peripheral blood mononuclear cells (hu-SGM3-PBMCs). All models exhibited infectious viruses in blood confirmed by plaque assay, but mice expressing human cytokines showed higher viremia compared to conventional NSG mice. The hu-SGM3-PBMCs model developed lethal infections, showing a significant increase in viremia and clinical signs. A detectable human cytokine response was observed in all the DENV-2-infected humanized mouse models. In conclusion, humanized NOD-derived mouse models expressing human cytokines offer a relevant platform for the study of dengue pathogenesis and antiviral therapies. Full article

(This article belongs to the Special Issue Emerging Arboviruses: Epidemiology, Vector Dynamics, and Pathogenesis)

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12 pages, 1161 KiB

Open AccessEditor’s ChoiceArticle

Investigating the Hepatitis E Virus (HEV) Diversity in Rat Reservoirs from Northern Italy

by Luca De Sabato, Marina Monini, Roberta Galuppi, Filippo Maria Dini, Giovanni Ianiro, Gabriele Vaccari, Fabio Ostanello and Ilaria Di Bartolo

Pathogens 2024, 13(8), 633; https://doi.org/10.3390/pathogens13080633 - 29 Jul 2024

Cited by 2 | Viewed by 1788

Abstract

Hepatitis E virus belonging to the Rocahepevirus ratti species, genotype HEV-C1, has been extensively reported in rats in Europe, Asia and North America. Recently, human cases of hepatitis associated with HEV-C1 infection have been reported, but the zoonotic nature of rat-HEV remains controversial. [...] Read more.

Hepatitis E virus belonging to the Rocahepevirus ratti species, genotype HEV-C1, has been extensively reported in rats in Europe, Asia and North America. Recently, human cases of hepatitis associated with HEV-C1 infection have been reported, but the zoonotic nature of rat-HEV remains controversial. The transmission route of rat-HEV is unidentified and requires further investigation. The HEV strains of the Paslahepevirus balayani species, belonging to the same Hepeviridae family, and including the zoonotic genotype HEV-3 usually found in pigs, have also sporadically been identified in rats. We sampled 115 rats (liver, lung, feces) between 2020 and 2023 in Northeast Italy and the HEV detection was carried out by using Reverse Transcription PCR. HEV RNA was detected in 3/115 (2.6%) rats who tested positive for HEV-C1 strains in paired lung, intestinal contents and liver samples. Overall, none tested positive for the Paslahepevirus balayani strains. In conclusion, our results confirm the presence of HEV-rat in Italy with a prevalence similar to previous studies but show that there is a wide heterogeneity of strains in circulation. The detection of HEV-C1 genotype of Rocahepevirus ratti species in some human cases of acute hepatitis suggests that HEV-C1 may be an underestimated source of human infections. This finding, with the geographically widespread detection of HEV-C1 in rats, raises questions about the role of rats as hosts for both HEV-C1 and HEV-3 and the possibility of zoonotic transmission. Full article

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34 pages, 15774 KiB

Open AccessEditor’s ChoiceReview

Parvoviruses of Aquatic Animals

by Frederick Kibenge, Molly Kibenge, Marco Montes de Oca and Marcos Godoy

Pathogens 2024, 13(8), 625; https://doi.org/10.3390/pathogens13080625 - 26 Jul 2024

Viewed by 2562

Abstract

Family Parvoviridae consists of small, non-enveloped viruses with linear, single-stranded DNA genomes of approximately 4-6 kilobases, subdivided into three subfamilies, Parvovirinae, Densovirinae, and Hamaparvovirinae, and unassigned genus Metalloincertoparvovirus. Parvoviruses of aquatic animals infect crustaceans, mollusks, and finfish. This review describes [...] Read more.

Family Parvoviridae consists of small, non-enveloped viruses with linear, single-stranded DNA genomes of approximately 4-6 kilobases, subdivided into three subfamilies, Parvovirinae, Densovirinae, and Hamaparvovirinae, and unassigned genus Metalloincertoparvovirus. Parvoviruses of aquatic animals infect crustaceans, mollusks, and finfish. This review describes these parvoviruses, which are highly host-specific and associated with mass morbidity and mortality in both farmed and wild aquatic animals. They include Cherax quadricarinatus densovirus (CqDV) in freshwater crayfish in Queensland, Australia; sea star-associated densovirus (SSaDV) in sunflower sea star on the Northeastern Pacific Coast; Clinch densovirus 1 in freshwater mussels in the Clinch River, Virginia, and Tennessee, USA, in subfamily Densovirinae; hepatopancreatic parvovirus (HPV) and infectious hypodermal and hematopoietic necrosis virus (IHHNV) in farmed shrimp worldwide; Syngnathid ichthamaparvovirus 1 in gulf pipefish in the Gulf of Mexico and parts of South America; tilapia parvovirus (TiPV) in farmed tilapia in China, Thailand, and India, in the subfamily Hamaparvovirinae; and Penaeus monodon metallodensovirus (PmMDV) in Vietnamese P. monodon, in unassigned genus Metalloincertoparvovirus. Also included in the family Parvoviridae are novel parvoviruses detected in both diseased and healthy animals using metagenomic sequencing, such as zander parvovirus from zander in Hungary and salmon parvovirus from sockeye salmon smolts in British Columbia, Canada. Full article

(This article belongs to the Special Issue Virulence Mechanisms, Detection and Control of Aquatic Animal Viruses: 2nd Edition)

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13 pages, 725 KiB

Open AccessEditor’s ChoiceArticle

Multidrug-Resistant Escherichia coli Accumulated by Freshwater Bivalves: An Underestimated Risk for Public Health?

by Joana C. L. Martins, Ana Gonçalves, Conceição Fernandes, Edna Cabecinha, Sandra Monteiro, Hugo Guedes, Gonçalo Almeida, Juliana Garcia, Gabriela J. da Silva, Simone Varandas and Maria J. Saavedra

Pathogens 2024, 13(8), 617; https://doi.org/10.3390/pathogens13080617 - 25 Jul 2024

Cited by 1 | Viewed by 1591

Abstract

As bioindicators, freshwater bivalves are crucial for the assessment of the contamination impact on different levels of biological integration. Escherichia coli is used as a bioindicator of water fecal contamination, representing a critical global concern, especially with the rise of multidrug-resistant (MDR) strains. [...] Read more.

As bioindicators, freshwater bivalves are crucial for the assessment of the contamination impact on different levels of biological integration. Escherichia coli is used as a bioindicator of water fecal contamination, representing a critical global concern, especially with the rise of multidrug-resistant (MDR) strains. Phylogenetic diversity, pathotypic characterization, and antibiotic resistance profiles of E. coli isolated from freshwater bivalves (Anodonta anatina) were assessed. Samples were collected from the Tua River in Northern Portugal, from two different sites, Chelas and Barcel, representing different degrees of contamination. Antimicrobial susceptibility testing was performed by the disk diffusion method, and characterizations of the phylogenetic groups and pathotypes were assessed by PCR-multiplex and real-time PCR-multiplex, respectively. Results showed that 60% of isolates were characterized as MDR, including resistance to carbapenems, considered the last resort against multidrug-resistant bacteria. Within this study, it was also possible to verify the antimicrobial resistance (AMR) profile differences between the two sampling sites, with bivalve isolates from the Chelas site showing a higher percentage of antibiotic resistance. Among the E. coli isolates, the highest prevalence (55%) was observed in group B1, followed by group D or E (15%), group A (10%), and group E or Clade I (10%). None of the isolates were classified as diarrheagenic E. coli (DEC). This work highlights the potential transmission of antimicrobial-resistant bacteria through bivalves in the food chain. The ‘One Health’ approach is crucial for combating antimicrobial resistance, namely in edible freshwater species, emphasizing active surveillance to protect human, animal, and environmental health against the spread of antibiotic-resistant bacteria in aquatic environments. Full article

(This article belongs to the Section Bacterial Pathogens)

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18 pages, 2594 KiB

Open AccessEditor’s ChoiceArticle

Comparative Genomic Analysis of Prophages in Human Vaginal Isolates of Streptococcus agalactiae

by Caitlin S. Wiafe-Kwakye, Andrew Fournier, Hannah Maurais, Katie J. Southworth, Sally D. Molloy and Melody N. Neely

Pathogens 2024, 13(8), 610; https://doi.org/10.3390/pathogens13080610 - 23 Jul 2024

Cited by 1 | Viewed by 1826

Abstract

Prophages, viral genomes integrated into bacterial genomes, are known to enhance bacterial colonization, adaptation, and ecological fitness, providing a better chance for pathogenic bacteria to disseminate and cause infection. Streptococcus agalactiae (Group B Streptococcus or GBS) is a common bacterium found colonizing the [...] Read more.

Prophages, viral genomes integrated into bacterial genomes, are known to enhance bacterial colonization, adaptation, and ecological fitness, providing a better chance for pathogenic bacteria to disseminate and cause infection. Streptococcus agalactiae (Group B Streptococcus or GBS) is a common bacterium found colonizing the genitourinary tract of humans. However, GBS-colonized pregnant women are at risk of passing the organism to the neonate, where it can cause severe infections. GBS typically encode one or more prophages in their genomes, yet their role in pathogen fitness and virulence has not yet been described. Sequencing and bioinformatic analysis of the genomic content of GBS human isolates identified 42 complete prophages present in their genomes. Comparative genomic analyses of the prophage sequences revealed that the prophages could be classified into five distinct clusters based on their genomic content, indicating significant diversity in their genetic makeup. Prophage diversity was also identified across GBS capsule serotypes, sequence types (STs), and clonal clusters (CCs). Comprehensive genomic annotation revealed that all GBS strains encode paratox, a protein that prevents the uptake of DNA in Streptococcus, either on the chromosome, on the prophage, or both, and each prophage genome has at least one toxin-antitoxin system. Full article

(This article belongs to the Section Bacterial Pathogens)

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16 pages, 1969 KiB

Open AccessEditor’s ChoiceReview

Interaction between Intestinal Parasites and the Gut Microbiota: Implications for the Intestinal Immune Response and Host Defence

by Jensine A. Grondin, Asif Jamal, Sadrina Mowna, Tyler Seto and Waliul I. Khan

Pathogens 2024, 13(8), 608; https://doi.org/10.3390/pathogens13080608 - 23 Jul 2024

Cited by 8 | Viewed by 6692

Abstract

Intestinal parasites, including helminths and protozoa, account for a significant portion of the global health burden. The gastrointestinal (GI) tract not only serves as the stage for these parasitic infections but also as the residence for millions of microbes. As the intricacies of [...] Read more.

Intestinal parasites, including helminths and protozoa, account for a significant portion of the global health burden. The gastrointestinal (GI) tract not only serves as the stage for these parasitic infections but also as the residence for millions of microbes. As the intricacies of the GI microbial milieu continue to unfold, it is becoming increasingly apparent that the interactions between host, parasite, and resident microbes help dictate parasite survival and, ultimately, disease outcomes. Across both clinical and experimental models, intestinal parasites have been shown to impact microbial composition and diversity. Reciprocally, microbes can directly influence parasitic survival, colonization and expulsion. The gut microbiota can also indirectly impact parasites through the influence and manipulation of the host. Studying this host–parasite–microbiota axis may help bring about novel therapeutic strategies for intestinal parasitic infection as well as conditions such as inflammatory bowel disease (IBD). In this review, we explore the relationship between intestinal parasites, with a particular focus on common protozoa and helminths, and the gut microbiota, and how these interactions can influence the host defence and intestinal immune response. We will also explore the impact of this tripartite relationship in a clinical setting and its broader implications for human health. Full article

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10 pages, 2282 KiB

Open AccessEditor’s ChoiceArticle

Wolbachia Promotes an Anti-Angiogenic Response Using an In Vitro Model of Vascular Endothelial Cells in Relation to Heartworm Disease

by Manuel Collado-Cuadrado, Claudia Alarcón-Torrecillas, Iván Rodríguez-Escolar, Alfonso Balmori-de la Puente, Elena Infante González-Mohino, Miguel Pericacho and Rodrigo Morchón

Pathogens 2024, 13(7), 603; https://doi.org/10.3390/pathogens13070603 - 22 Jul 2024

Cited by 2 | Viewed by 1343

Abstract

Heartworm disease caused by Dirofilaria immitis is a vector-borne zoonotic disease responsible for the infection of mainly domestic dogs and cats, or these are those for which the most data are known. Humans are an accidental host where a benign, asymptomatic pulmonary nodule [...] Read more.

Heartworm disease caused by Dirofilaria immitis is a vector-borne zoonotic disease responsible for the infection of mainly domestic dogs and cats, or these are those for which the most data are known. Humans are an accidental host where a benign, asymptomatic pulmonary nodule may originate. Dirofilaria immitis also harbours the endosymbiont bacteria of the genus Wolbachia, which play a role in moulting, embryogenesis, inflammatory pathology, and immune response. When Wolbachia sp. is released into the bloodstream, endothelial and pulmonary damage is exacerbated, further encouraging thrombus formation and pulmonary hypertension, facilitating congestive heart failure and death of the animal. Previous studies have shown that parasite excretory/secretory products are able to activate the pro-angiogenic pathway (formation of new vessels) to facilitate parasite survival. The aim of this study was to analyse the role of Wolbachia sp. and its relationship with the cellular processes and the angiogenic pathway in a model of human endothelial cells in vitro. The use of recombinant Wolbachia Surface Protein (rWSP) showed that its stimulation exerted an anti-angiogenic effect by detecting an increase in the production of VEGFR-1/sFlt1 and sEndoglin and did not affect the production of VEGFR-2 and mEndoglin (pro-angiogenic molecules). Furthermore, it did not stimulate cell proliferation or migration, although it did negatively stimulate the formation of pseudocapillaries, slowing down this process. These cellular processes are directly related to the angiogenic pathway so, with these results, we can conclude that Wolbachia sp. is related to the stimulation of the anti-angiogenic pathway, not facilitating the survival of D. immitis in vascular endothelium. Full article

(This article belongs to the Special Issue Dirofilariosis and Angiostrongylosis in Animals and Humans: A Global Challenge)

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16 pages, 2488 KiB

Open AccessEditor’s ChoiceArticle

The Non-Histone Protein FgNhp6 Is Involved in the Regulation of the Development, DON Biosynthesis, and Virulence of Fusarium graminearum

by Jiakuo Cao, Junbo Lv, Limin Zhang, Heng Li, Hao Ma, Yanxiang Zhao and Jinguang Huang

Pathogens 2024, 13(7), 592; https://doi.org/10.3390/pathogens13070592 - 16 Jul 2024

Cited by 1 | Viewed by 1344

Abstract

Fusarium graminearum is the primary causative agent of Fusarium head blight (FHB), a devastating disease affecting cereals globally. The high-mobility group (HMG) of non-histone proteins constitutes vital architectural elements within chromatin, playing diverse roles in various biological processes in eukaryotic cells. Nonetheless, the [...] Read more.

Fusarium graminearum is the primary causative agent of Fusarium head blight (FHB), a devastating disease affecting cereals globally. The high-mobility group (HMG) of non-histone proteins constitutes vital architectural elements within chromatin, playing diverse roles in various biological processes in eukaryotic cells. Nonetheless, the specific functions of HMG proteins in F. graminearum have yet to be elucidated. Here, we identified 10 HMG proteins in F. graminearum and extensively characterized the biological roles of one HMGB protein, FgNhp6. We constructed the FgNhp6 deletion mutant and its complementary strains. With these strains, we confirmed the nuclear localization of FgNhp6 and discovered that the absence of FgNhp6 led to reduced radial growth accompanied by severe pigmentation defects, a significant reduction in conidial production, and a failure to produce perithecia. The ∆FgNhp6 mutant exhibited a markedly reduced pathogenicity on wheat coleoptiles and spikes, coupled with a significant increase in deoxynivalenol production. An RNA sequencing (RNA-seq) analysis indicated that FgNhp6 deletion influenced a wide array of metabolic pathways, particularly affecting several secondary metabolic pathways, such as sterol biosynthesis and aurofusarin biosynthesis. The findings of this study highlight the essential role of FgNhp6 in the regulation of the asexual and sexual reproduction, deoxynivalenol (DON) production, and pathogenicity of F. graminearum. Full article

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31 pages, 4696 KiB

Open AccessEditor’s ChoiceReview

Host Innate Antiviral Response to Influenza A Virus Infection: From Viral Sensing to Antagonism and Escape

by Wenlong An, Simran Lakhina, Jessica Leong, Kartik Rawat and Matloob Husain

Pathogens 2024, 13(7), 561; https://doi.org/10.3390/pathogens13070561 - 3 Jul 2024

Cited by 6 | Viewed by 5448

Abstract

Influenza virus possesses an RNA genome of single-stranded, negative-sensed, and segmented configuration. Influenza virus causes an acute respiratory disease, commonly known as the “flu” in humans. In some individuals, flu can lead to pneumonia and acute respiratory distress syndrome. Influenza A virus (IAV) [...] Read more.

Influenza virus possesses an RNA genome of single-stranded, negative-sensed, and segmented configuration. Influenza virus causes an acute respiratory disease, commonly known as the “flu” in humans. In some individuals, flu can lead to pneumonia and acute respiratory distress syndrome. Influenza A virus (IAV) is the most significant because it causes recurring seasonal epidemics, occasional pandemics, and zoonotic outbreaks in human populations, globally. The host innate immune response to IAV infection plays a critical role in sensing, preventing, and clearing the infection as well as in flu disease pathology. Host cells sense IAV infection through multiple receptors and mechanisms, which culminate in the induction of a concerted innate antiviral response and the creation of an antiviral state, which inhibits and clears the infection from host cells. However, IAV antagonizes and escapes many steps of the innate antiviral response by different mechanisms. Herein, we review those host and viral mechanisms. This review covers most aspects of the host innate immune response, i.e., (1) the sensing of incoming virus particles, (2) the activation of downstream innate antiviral signaling pathways, (3) the expression of interferon-stimulated genes, (4) and viral antagonism and escape. Full article

(This article belongs to the Special Issue Host Immune Responses to RNA Viruses, 2nd Edition)

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24 pages, 3727 KiB

Open AccessEditor’s ChoiceReview

Zika Virus Neuropathogenesis—Research and Understanding

by Anna D. Metzler and Hengli Tang

Pathogens 2024, 13(7), 555; https://doi.org/10.3390/pathogens13070555 - 2 Jul 2024

Cited by 2 | Viewed by 4300

Abstract

Zika virus (ZIKV), a mosquito-borne flavivirus, is prominently associated with microcephaly in babies born to infected mothers as well as Guillain-Barré Syndrome in adults. Each cell type infected by ZIKV—neuronal cells (radial glial cells, neuronal progenitor cells, astrocytes, microglia cells, and glioblastoma stem [...] Read more.

Zika virus (ZIKV), a mosquito-borne flavivirus, is prominently associated with microcephaly in babies born to infected mothers as well as Guillain-Barré Syndrome in adults. Each cell type infected by ZIKV—neuronal cells (radial glial cells, neuronal progenitor cells, astrocytes, microglia cells, and glioblastoma stem cells) and non-neuronal cells (primary fibroblasts, epidermal keratinocytes, dendritic cells, monocytes, macrophages, and Sertoli cells)—displays its own characteristic changes to their cell physiology and has various impacts on disease. Here, we provide an in-depth review of the ZIKV life cycle and its cellular targets, and discuss the current knowledge of how infections cause neuropathologies, as well as what approaches researchers are currently taking to further advance such knowledge. A key aspect of ZIKV neuropathogenesis is virus-induced neuronal apoptosis via numerous mechanisms including cell cycle dysregulation, mitochondrial fragmentation, ER stress, and the unfolded protein response. These, in turn, result in the activation of p53-mediated intrinsic cell death pathways. A full spectrum of infection models including stem cells and co-cultures, transwells to simulate blood–tissue barriers, brain-region-specific organoids, and animal models have been developed for ZIKV research. Full article

(This article belongs to the Special Issue Neuropathogenesis of Arboviruses)

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8 pages, 366 KiB

Open AccessEditor’s ChoiceReview

High HTLV-1 Proviral Load Predates and Predicts HTLV-1-Associated Disease: Literature Review and the London Experience

by Graham P. Taylor, William Evans and Carolina Rosadas

Pathogens 2024, 13(7), 553; https://doi.org/10.3390/pathogens13070553 - 1 Jul 2024

Cited by 2 | Viewed by 1990

Abstract

Human T cell lymphotropic virus type 1 (HTLV-1) is a retrovirus that infects lymphocytes and causes severe diseases. HTLV-1 proviral load (PVL), i.e., the number of host cells that carry HTLV-1 proviral DNA integrated into their genome, can be measured in peripheral blood [...] Read more.

Human T cell lymphotropic virus type 1 (HTLV-1) is a retrovirus that infects lymphocytes and causes severe diseases. HTLV-1 proviral load (PVL), i.e., the number of host cells that carry HTLV-1 proviral DNA integrated into their genome, can be measured in peripheral blood mononuclear cells (PBMCs) using quantitative polymerase chain reaction. In this narrative review, we discuss the usefulness of HTLV-1 PVL quantification and share our experience acquired during more than 30 years of follow-up of people living with HTLV-1 in the UK. Patients with HTLV-1-associated myelopathy have higher PVL than those with asymptomatic infection. This is consistent across studies in different countries. High PVL predates symptom onset for both inflammatory and proliferative diseases. High PVL is essential but not sufficient for the development of HTLV-1-associated diseases. Therefore, PVL quantification can be used to support the care of people living with HTLV-1 by identifying those most at risk of HTLV-1-associated diseases. Full article

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

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20 pages, 1978 KiB

Open AccessEditor’s ChoiceArticle

Water Stress and Black Cutworm Feeding Modulate Plant Response in Maize Colonized by Metarhizium robertsii

by Imtiaz Ahmad, Maria del Mar Jimenez-Gasco and Mary E. Barbercheck

Pathogens 2024, 13(7), 544; https://doi.org/10.3390/pathogens13070544 - 27 Jun 2024

Cited by 2 | Viewed by 1445

Abstract

Plants face many environmental challenges and have evolved different strategies to defend against stress. One strategy is the establishment of mutualistic associations with endophytic microorganisms which contribute to plant defense and promote plant growth. The fungal entomopathogen Metarhizium robertsii is also an endophyte [...] Read more.

Plants face many environmental challenges and have evolved different strategies to defend against stress. One strategy is the establishment of mutualistic associations with endophytic microorganisms which contribute to plant defense and promote plant growth. The fungal entomopathogen Metarhizium robertsii is also an endophyte that can provide plant-protective and growth-promoting benefits to the host plant. We conducted a greenhouse experiment in which we imposed stress from deficit and excess soil moisture and feeding by larval black cutworm (BCW), Agrotis ipsilon, to maize plants that were either inoculated or not inoculated with M. robertsii (Mr). We evaluated plant growth and defense indicators to determine the effects of the interaction between Mr, maize, BCW feeding, and water stress. There was a significant effect of water treatment, but no effect of Mr treatment, on plant chlorophyl, height, and dry biomass. There was no effect of water or Mr treatment on damage caused by BCW feeding. There was a significant effect of water treatment, but not Mr treatment, on the expression of bx7 and rip2 genes and on foliar content of abscisic acid (ABA), 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA), and gibberellin 19 (GA19), whereas GA53 was modulated by Mr treatment. Foliar content of GA19 and cis-Zeatin (cZ) was modulated by BCW feeding. In a redundancy analysis, plant phenology, plant nutrient content, and foliar DIMBOA and ABA content were most closely associated with water treatments. This study contributes toward understanding the sophisticated stress response signaling and endophytic mutualisms in crops. Full article

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19 pages, 3407 KiB

Open AccessEditor’s ChoiceSystematic Review

Difference in the Intestinal Microbiota between Breastfeed Infants and Infants Fed with Artificial Milk: A Systematic Review

by Francesco Inchingolo, Angelo Michele Inchingolo, Giulia Latini, Laura Ferrante, Elisabetta de Ruvo, Merigrazia Campanelli, Marialuisa Longo, Andrea Palermo, Alessio Danilo Inchingolo and Gianna Dipalma

Pathogens 2024, 13(7), 533; https://doi.org/10.3390/pathogens13070533 - 24 Jun 2024

Cited by 10 | Viewed by 4377

Abstract

The gut microbiota (GM) plays a crucial role in human health, particularly during the first years of life. Differences in GM between breastfed and formula (F)-fed infants may influence long-term health outcomes. This systematic review aims to compare the gut microbiota of breastfed [...] Read more.

The gut microbiota (GM) plays a crucial role in human health, particularly during the first years of life. Differences in GM between breastfed and formula (F)-fed infants may influence long-term health outcomes. This systematic review aims to compare the gut microbiota of breastfed infants with that of F-fed infants and to evaluate the clinical implications of these differences. We searched databases on Scopus, Web of Science, and Pubmed with the following keywords: “gut microbiota”, “gut microbiome”, and “neonatal milk”. The inclusion criteria were articles relating to the analysis of the intestinal microbiome of newborns in relation to the type of nutrition, clinical studies or case series, excluding reviews, meta-analyses, animal models, and in vitro studies. The screening phase ended with the selection of 13 publications for this work. Breastfed infants showed higher levels of beneficial bacteria such as Bifidobacterium and Lactobacillus, while F-fed infants had a higher prevalence of potentially pathogenic bacteria, including Clostridium difficile and Enterobacteriaceae. Infant feeding type influences the composition of oral GM significantly. Breastfeeding promotes a healthier and more diverse microbial ecosystem, which may offer protective health benefits. Future research should explore strategies to improve the GM of F-fed infants and understand the long-term health implications. Full article

(This article belongs to the Special Issue Oral Microbiome and Human Systemic Health)

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12 pages, 255 KiB

Open AccessEditor’s ChoiceArticle

Prevalence of Subgingival Aggregatibacter actinomycetemcomitans: Descriptive Cross-Sectional Study

by Nabil Khzam, Omar Kujan, Dorte Haubek, Aysen Arslan, Anders Johansson, Jan Oscarsson, Zeinab Razooqi and Leticia Algarves Miranda

Pathogens 2024, 13(7), 531; https://doi.org/10.3390/pathogens13070531 - 24 Jun 2024

Cited by 4 | Viewed by 1759

Abstract

This paper aims to investigate the presence of Aggregatibacter actinomycetemcomitans and to assess potential indicators of the risk of severe form(s) of periodontitis. A descriptive cross-sectional study of 156 consecutive patients with periodontitis was conducted. Subgingival plaque samples were collected from the participants. [...] Read more.

This paper aims to investigate the presence of Aggregatibacter actinomycetemcomitans and to assess potential indicators of the risk of severe form(s) of periodontitis. A descriptive cross-sectional study of 156 consecutive patients with periodontitis was conducted. Subgingival plaque samples were collected from the participants. The identification of A. actinomycetemcomitans was performed using quantitative polymerase chain reaction. A descriptive analysis, a chi-square test, and a binary logistic regression statistical evaluation were performed. The prevalence of A. actinomycetemcomitans in this population of 156 participants was 17.30% (27 patients). The prevalence of stage-III periodontitis was 75.6% and greater in older men, while the prevalence of stage-IV periodontitis was 22.4% and greater in younger women. We observed a significant relation between the risk of severe periodontitis (stage-IV) and poor oral hygiene (p = 0.006), attendance at dental appointments (p ≤ 0.001), and familial history of periodontitis (p = 0.032). In conclusion, twenty-seven individuals were positive for A. actinomycetemcomitans. Poor oral hygiene, family history of periodontitis, and irregular attendance at dental appointments were identified as potential risk factors for severe periodontitis in this cohort. Full article

(This article belongs to the Special Issue Oral Microbiome and Human Systemic Health)

16 pages, 14810 KiB

Open AccessEditor’s ChoiceArticle

Upregulation of Neuroinflammation-Associated Genes in the Brain of SARS-CoV-2-Infected Mice

by Soo-Jin Oh, Pratima Kumari, Tabassum Tasnim Auroni, Shannon Stone, Heather Pathak, Amany Elsharkawy, Janhavi Prasad Natekar, Ok Sarah Shin and Mukesh Kumar

Pathogens 2024, 13(7), 528; https://doi.org/10.3390/pathogens13070528 - 22 Jun 2024

Cited by 3 | Viewed by 2134

Abstract

Neurological manifestations are a significant complication of coronavirus disease 2019 (COVID-19), but the underlying mechanisms are yet to be understood. Recently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced neuroinvasion and encephalitis were observed in K18-hACE2 mice, leading to mortality. Our goal in this [...] Read more.

Neurological manifestations are a significant complication of coronavirus disease 2019 (COVID-19), but the underlying mechanisms are yet to be understood. Recently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced neuroinvasion and encephalitis were observed in K18-hACE2 mice, leading to mortality. Our goal in this study was to gain insights into the molecular pathogenesis of neurological manifestations in this mouse model. To analyze differentially expressed genes (DEGs) in the brains of mice following SARS-CoV-2 infection, we performed NanoString gene expression analysis using three individual animal samples at 1, 3, and 6 days post-infection. We identified the DEGs by comparing them to animals that were not infected with the virus. We found that genes upregulated at day 6 post-infection were mainly associated with Toll-like receptor (TLR) signaling, RIG-I-like receptor (RLR) signaling, and cell death pathways. However, downregulated genes were associated with neurodegeneration and synaptic signaling pathways. In correlation with gene expression profiles, a multiplexed immunoassay showed the upregulation of multiple cytokines and chemokines involved in inflammation and cell death in SARS-CoV-2-infected brains. Furthermore, the pathway analysis of DEGs indicated a possible link between TLR2-mediated signaling pathways and neuroinflammation, as well as pyroptosis and necroptosis in the brain. In conclusion, our work demonstrates neuroinflammation-associated gene expression profiles, which can provide key insight into the severe disease observed in COVID-19 patients. Full article

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26 pages, 1057 KiB

Open AccessEditor’s ChoiceReview

Advances in Laboratory Diagnosis of Coronavirus Infections in Cattle

by Shaun van den Hurk, Girija Regmi, Hemant K. Naikare and Binu T. Velayudhan

Pathogens 2024, 13(7), 524; https://doi.org/10.3390/pathogens13070524 - 21 Jun 2024

Cited by 3 | Viewed by 2315

Abstract

Coronaviruses cause infections in humans and diverse species of animals and birds with a global distribution. Bovine coronavirus (BCoV) produces predominantly two forms of disease in cattle: a respiratory form and a gastrointestinal form. All age groups of cattle are affected by the [...] Read more.

Coronaviruses cause infections in humans and diverse species of animals and birds with a global distribution. Bovine coronavirus (BCoV) produces predominantly two forms of disease in cattle: a respiratory form and a gastrointestinal form. All age groups of cattle are affected by the respiratory form of coronavirus, whereas the gastroenteric form causes neonatal diarrhea or calf scours in young cattle and winter dysentery in adult cattle. The tremendous impacts of bovine respiratory disease and the associated losses are well-documented and underscore the importance of this pathogen. Beyond this, studies have demonstrated significant impacts on milk production associated with outbreaks of winter dysentery, with up to a 30% decrease in milk yield. In North America, BCoV was identified for the first time in 1972, and it continues to be a significant economic concern for the cattle industry. A number of conventional and molecular diagnostic assays are available for the detection of BCoV from clinical samples. Conventional assays for BCoV detection include virus isolation, which is challenging from clinical samples, electron microscopy, fluorescent antibody assays, and various immunoassays. Molecular tests are mainly based on nucleic acid detection and predominantly include conventional and real-time polymerase chain reaction (PCR) assays. Isothermal amplification assays and genome sequencing have gained increased interest in recent years for the detection, characterization, and identification of BCoV. It is believed that isothermal amplification assays, such as loop-mediated isothermal amplification and recombinase polymerase amplification, among others, could aid the development of barn-side point-of-care tests for BCoV. The present study reviewed the literature on coronavirus infections in cattle from the last three and a half decades and presents information mainly on the current and advancing diagnostics in addition to epidemiology, clinical presentations, and the impact of the disease on the cattle industry. Full article

(This article belongs to the Special Issue Diagnostics of Emerging and Re-Emerging Pathogens)

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13 pages, 1607 KiB

Open AccessEditor’s ChoiceArticle

Humoral Immune Response in Immunized Sheep with Bovine Coronavirus Glycoproteins Delivered via an Adenoviral Vector

by Annamaria Pratelli, Paolo Capozza, Sergio Minesso, Maria Stella Lucente, Francesco Pellegrini, Maria Tempesta, Valentina Franceschi, Canio Buonavoglia and Gaetano Donofrio

Pathogens 2024, 13(7), 523; https://doi.org/10.3390/pathogens13070523 - 21 Jun 2024

Cited by 3 | Viewed by 1288

Abstract

Bovine coronavirus (BCoV) is distributed globally and mainly causes different clinical manifestations: enteric diarrhea in calves, winter dysentery in adults, and respiratory symptoms in cattle of all ages. Low mortality and high morbidity are the hallmarks of BCoV infection, usually associated with substantial [...] Read more.

Bovine coronavirus (BCoV) is distributed globally and mainly causes different clinical manifestations: enteric diarrhea in calves, winter dysentery in adults, and respiratory symptoms in cattle of all ages. Low mortality and high morbidity are the hallmarks of BCoV infection, usually associated with substantial economic losses for the livestock industry. Vaccination, combined with the implementation of biosecurity measures, is the key strategy for the prevention of infections. This pilot study evaluates the immunogenicity of a recombinant vaccine containing two BCoV antigens (S and M) in sheep, compared to vaccines containing only the M or S protein. Three groups of sheep were inoculated intramuscularly at day 0 and day 21 with recombinant adenoviruses expressing BCoV S protein (AdV-BCoV-S), BCoV M protein (AdV-BCoV-M), or both proteins (AdV-BCoV-S + M). Serum antibodies were evaluated using immunofluorescence (IF) and serum neutralization (SN) tests. Moderate seroconversion was observed by day 21, but serum antibodies detected via SN increased from 1:27.5 (day 21) to 1:90 (day 28) in sheep inoculated with the recombinant AdV expressing both the S- and M-BCoV proteins. Based on the SN results, a repeated-measures ANOVA test indicated a more significant difference in immune response between the three groups (F = 20.47; p < 0.001). The experimental investigation produced satisfactory results, highlighting that the S + M recombinant vaccine was immunogenic, stimulating a valid immune response. Despite some inherent limitations, including a small sample size and the absence of challenge tests, the study demonstrated the efficacy of the immune response induced via the recombinant vaccine containing both S and M proteins compared to that induced via the individual proteins S or M. Full article

(This article belongs to the Section Vaccines and Therapeutic Developments)

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12 pages, 1721 KiB

Open AccessEditor’s ChoiceArticle

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

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

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

Cited by 1 | Viewed by 1697

Abstract

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

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

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12 pages, 1504 KiB

Open AccessEditor’s ChoiceArticle

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

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

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

Viewed by 3026

Abstract

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

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

(This article belongs to the Section Viral Pathogens)

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13 pages, 1980 KiB

Open AccessEditor’s ChoiceArticle

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

by Antonio Doménech-Sánchez, Elena Laso and Sebastián Albertí

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

Viewed by 1697

Abstract

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

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

(This article belongs to the Section Bacterial Pathogens)

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31 pages, 4290 KiB

Open AccessEditor’s ChoiceReview

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

by Amerah Parveen and Amal Ali Elkordy

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

Cited by 2 | Viewed by 3097

Abstract

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

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

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

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15 pages, 1364 KiB

Open AccessEditor’s ChoiceArticle

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

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

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

Viewed by 2308

Abstract

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

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

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

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19 pages, 3010 KiB

Open AccessEditor’s ChoiceReview

Congenital Syphilis: A Re-Emerging but Preventable Infection

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

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

Cited by 4 | Viewed by 3751

Abstract

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

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

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

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13 pages, 411 KiB

Open AccessEditor’s ChoiceArticle

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

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

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

Cited by 1 | Viewed by 1729

Abstract

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

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

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

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14 pages, 2270 KiB

Open AccessEditor’s ChoiceArticle

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

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

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

Viewed by 1818

Abstract

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

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

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

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16 pages, 359 KiB

Open AccessEditor’s ChoiceReview

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

by Mary Garvey

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

Cited by 6 | Viewed by 3781

Abstract

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

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

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

13 pages, 2088 KiB

Open AccessEditor’s ChoiceArticle

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

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

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

Cited by 2 | Viewed by 2066

Abstract

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

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

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

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28 pages, 2086 KiB

Open AccessEditor’s ChoiceReview

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

by Damian Pietrzak, Julia Weronika Łuczak and Marcin Wiśniewski

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

Cited by 1 | Viewed by 2984

Abstract

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

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

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

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13 pages, 261 KiB

Open AccessEditor’s ChoiceReview

Human Cytomegalovirus Infection and Neurocognitive and Neuropsychiatric Health

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

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

Cited by 2 | Viewed by 3173

Abstract

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

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

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

15 pages, 5079 KiB

Open AccessEditor’s ChoiceArticle

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

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

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

Viewed by 1792

Abstract

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

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

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

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14 pages, 2428 KiB

Open AccessEditor’s ChoiceArticle

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

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

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

Cited by 2 | Viewed by 1963

Abstract

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

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

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

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12 pages, 480 KiB

Open AccessEditor’s ChoiceArticle

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

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

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

Cited by 1 | Viewed by 1614

Abstract

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

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

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

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14 pages, 967 KiB

Open AccessEditor’s ChoiceArticle

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

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

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

Cited by 4 | Viewed by 2960

Abstract

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

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

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

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9 pages, 468 KiB

Open AccessEditor’s ChoiceArticle

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

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

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

Cited by 3 | Viewed by 3007

Abstract

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

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

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

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12 pages, 3806 KiB

Open AccessEditor’s ChoiceArticle

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

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

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

Cited by 1 | Viewed by 2869

Abstract

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

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

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

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9 pages, 600 KiB

Open AccessEditor’s ChoiceArticle

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

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

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

Cited by 2 | Viewed by 2510

Abstract

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

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

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

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22 pages, 5093 KiB

Open AccessEditor’s ChoiceArticle

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

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

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

Cited by 3 | Viewed by 5294

Abstract

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

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

(This article belongs to the Section Parasitic Pathogens)

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14 pages, 1152 KiB

Open AccessEditor’s ChoiceReview

The Role of Prevotella Species in Female Genital Tract Infections

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

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

Cited by 2 | Viewed by 5698

Abstract

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

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

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20 pages, 1888 KiB

Open AccessEditor’s ChoiceReview

Hepatitis Delta Virus and Hepatocellular Carcinoma

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

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

Cited by 5 | Viewed by 2691

Abstract

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

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

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

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11 pages, 1569 KiB

Open AccessEditor’s ChoiceReview

Therapeutic Applications of Aggregatibacter actinomycetemcomitans Leukotoxin

by Scott C. Kachlany and Brian A. Vega

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

Cited by 2 | Viewed by 2205

Abstract

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

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

(This article belongs to the Special Issue Aggregatibacter actinomycetemcomitans: A D-3 (Dysbiosis, Damage, Disease) Periodontal Pathobiont)

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14 pages, 412 KiB

Open AccessEditor’s ChoiceReview

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

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

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

Cited by 7 | Viewed by 3841

Abstract

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

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

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

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20 pages, 1913 KiB

Open AccessEditor’s ChoiceReview

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

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

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

Cited by 5 | Viewed by 3381

Abstract

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

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

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

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12 pages, 1729 KiB

Open AccessEditor’s ChoiceArticle

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

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

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

Viewed by 1986

Abstract

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

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

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

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30 pages, 7697 KiB

Open AccessEditor’s ChoiceArticle

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

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

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

Cited by 4 | Viewed by 3033

Abstract

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

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

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

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15 pages, 1318 KiB

Open AccessEditor’s ChoiceReview

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

by Kay Choong See

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

Cited by 7 | Viewed by 5086

Abstract

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

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

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

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10 pages, 217 KiB

Open AccessEditor’s ChoiceArticle

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

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

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

Cited by 2 | Viewed by 2727

Abstract

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

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

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

12 pages, 859 KiB

Open AccessEditor’s ChoiceArticle

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

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

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

Viewed by 2218

Abstract

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

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

(This article belongs to the Section Viral Pathogens)

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52 pages, 1537 KiB

Open AccessEditor’s ChoiceReview

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

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

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

Cited by 8 | Viewed by 4577

Abstract

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

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

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

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18 pages, 288 KiB

Open AccessEditor’s ChoiceArticle

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

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

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

Cited by 3 | Viewed by 2343

Abstract

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

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

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

11 pages, 1395 KiB

Open AccessEditor’s ChoiceReview

Prospects for Controlling Hepatitis B Globally

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

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

Cited by 5 | Viewed by 3732

Abstract

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

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

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

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