Journal Description
Pathogens
Pathogens
is an international, peer-reviewed, open access journal on pathogens and pathogen-host interactions published monthly online by MDPI.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, Embase, PubAg, CaPlus / SciFinder, AGRIS, and other databases.
- Journal Rank: JCR - Q2 (Microbiology) / CiteScore - Q2 (General Immunology and Microbiology )
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 16.4 days after submission; acceptance to publication is undertaken in 2.6 days (median values for papers published in this journal in the second half of 2023).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
- Companion journals for Pathogens include: Parasitologia, Bacteria and Zoonotic Diseases.
Impact Factor:
3.7 (2022);
5-Year Impact Factor:
3.7 (2022)
Latest Articles
Peptide-Alkoxyamine Drugs: An Innovative Approach to Fight Schistosomiasis: “Digging Their Graves with Their Forks”
Pathogens 2024, 13(6), 482; https://doi.org/10.3390/pathogens13060482 (registering DOI) - 6 Jun 2024
Abstract
The expansion of drug resistant parasites sheds a serious concern on several neglected parasitic diseases. Our recent results on cancer led us to envision the use of peptide-alkoxyamines as a highly selective and efficient new drug against schistosome adult worms, the etiological agents
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The expansion of drug resistant parasites sheds a serious concern on several neglected parasitic diseases. Our recent results on cancer led us to envision the use of peptide-alkoxyamines as a highly selective and efficient new drug against schistosome adult worms, the etiological agents of schistosomiasis. Indeed, the peptide tag of the hybrid compounds can be hydrolyzed by worm’s digestive enzymes to afford a highly labile alkoxyamine which homolyzes spontaneously and instantaneously into radicals—which are then used as a drug against Schistosome adult parasites. This approach is nicely summarized as digging their graves with their forks. Several hybrid peptide-alkoxyamines were prepared and clearly showed an activity: two of the tested compounds kill 50% of the parasites in two hours at a concentration of 100 µg/mL. Importantly, the peptide and alkoxyamine fragments that are unable to generate alkyl radicals display no activity. This strong evidence validates the proposed mechanism: a specific activation of the prodrugs by the parasite proteases leading to parasite death through in situ alkyl radical generation.
Full article
(This article belongs to the Special Issue Human Parasitic Diseases: Challenges and Progress in Drug Discovery and Target Identification)
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Congenital Syphilis: A Re-Emerging but Preventable Infection
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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
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
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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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Open AccessArticle
Catalytic Differences between Flavohemoglobins of Giardia intestinalis and E. coli
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Sarah Hill, Isabelle Decorso, Novin Nezamololama, Zahra Babaei and Steven Patrick Rafferty
Pathogens 2024, 13(6), 480; https://doi.org/10.3390/pathogens13060480 - 6 Jun 2024
Abstract
The sole known heme enzyme of the parasitic protist Giardia intestinalis is a flavohemoglobin (gFlHb) that acts as a nitric oxide dioxygenase (NOD) and protects the organism from the free radical nitric oxide. To learn more about the properties of this enzyme, we
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The sole known heme enzyme of the parasitic protist Giardia intestinalis is a flavohemoglobin (gFlHb) that acts as a nitric oxide dioxygenase (NOD) and protects the organism from the free radical nitric oxide. To learn more about the properties of this enzyme, we measured its nitric oxide dioxygenase, NADH oxidase, and cytochrome c reductase activities and compared these to the activities of the E. coli flavohemoglobin (Hmp). The turnover number for the NOD activity of gFlHb (23 s−1) is about two-thirds of that of Hmp (34 s−1) at pH 6.5 and 37 °C. The two enzymes differ in their sensitivity towards molecules that act as heme ligands. For both gFlHb and Hmp, inhibition with miconazole, a large imidazole ligand, is adequately described by simple competitive inhibition, with KI = 10 μM and 0.27 μM for gFlHb and Hmp, respectively. Inhibition plots with the small ligand imidazole were biphasic, which is consistent with previous experiments with carbon monoxide as a probe that show that the active site of flavohemoglobins exists in two conformations. Interestingly, the largest difference is observed with nitrite, which, like imidazole, also shows a biphasic inhibition plot; however, nitrite inhibits gFlHb at sub-millimolar concentrations while Hmp is not significantly affected. NADH oxidase activity measured under aerobic conditions in the absence of nitric oxide for Hmp was more than twice the activity of gFlHb. The addition of 1 mM hydrogen peroxide in these assays stimulated the NADH oxidase activity of gFlHb but not Hmp. Both enzymes had nearly identical cytochrome c reductase activities but the extent of the contribution of indirect reduction by flavohemoglobin-generated superoxide was much lower with gFlHb (4% SOD-inhibited) than with Hmp (17% SOD-inhibited). Although the active sites of the two enzymes share the same highly conserved residues that are important for catalysis, differences in the distal ligand binding site may account for these differences in activity and sensitivity towards NOD inhibitors. The differences observed in the NADH oxidase and cytochrome c reductase assays suggest that gFlHb may have evolved to protect the protist, which lacks both superoxide dismutase and catalase, from the damaging effects of superoxide by minimizing its production and from peroxide by actively reducing it.
Full article
(This article belongs to the Special Issue Pathogenesis and Treatment of Giardiasis)
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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
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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
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
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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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Open AccessArticle
Comparative Analysis of Immune Gene Transcription in Sea Bream (Sparus aurata) Challenged with RGNNV or RGNNV/SJNNV Betanodaviruses
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Juan Gemez-Mata, Patricia Moreno, Daniel Alvarez-Torres, Esther Garcia-Rosado, Julia Bejar and M. Carmen Alonso
Pathogens 2024, 13(6), 478; https://doi.org/10.3390/pathogens13060478 - 4 Jun 2024
Abstract
Gilthead sea bream and European sea bass display different resistance–susceptibility patterns during infection with different nervous necrosis virus (NNV) species, which may derive from differences in the triggered immune response. Based on this premise, we analysed the transcription of several selected immune-related genes
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Gilthead sea bream and European sea bass display different resistance–susceptibility patterns during infection with different nervous necrosis virus (NNV) species, which may derive from differences in the triggered immune response. Based on this premise, we analysed the transcription of several selected immune-related genes in sea bream experimentally infected with NNV isolates obtained from sea bass (DlNNV, RGNNV) or sea bream (SaNNV, RGNNV/SJNNV). Viral replication only occurred in SaNNV-inoculated fish; therefore, the differences between the immune response elicited by both viruses may be the key to understanding the mechanism behind the inhibition of DlNNV replication. Principal component analysis clustered samples according to the viral isolate from 1 day post infection onwards and evidenced differences in the immune response against both viruses, even though no mortalities or symptoms were recorded. The response against DlNNV is characterized by higher rtp3 transcription early after the infection, longer-lasting il-10 transcription and stronger induction of casp1 and hsp70. These genes should be targets for future studies in order to elucidate their role in hampering NNV replication in sea bream, which is essential for developing effective prophylactic measures.
Full article
(This article belongs to the Section Viral Pathogens)
Open AccessArticle
Evaluation of the Local and Peripheral Immune Responses in Patients with Cystic Echinococcosis
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Linda Petrone, Saeid Najafi-Fard, Laura Falasca, Settimia Sbarra, Antonella Teggi, Emanuele Nicastri, Lucia Rosalba Grillo, Mirco Burocchi, Giuseppe Maria Ettorre, Alessandra Ludovisi, Daniele Colombo, Franca Del Nonno and Delia Goletti
Pathogens 2024, 13(6), 477; https://doi.org/10.3390/pathogens13060477 - 4 Jun 2024
Abstract
Background: Cystic echinococcosis (CE) cysts may persist for decades because of immune modulation mechanisms. Here, we characterize the cysts and the blood immune responses in patients with CE. Methods: We enrolled 61 patients with CE and 19 control subjects. We received tissue samples
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Background: Cystic echinococcosis (CE) cysts may persist for decades because of immune modulation mechanisms. Here, we characterize the cysts and the blood immune responses in patients with CE. Methods: We enrolled 61 patients with CE and 19 control subjects. We received tissue samples from seven patients with CE and a control subject requiring liver cystectomy. The immunohistochemistry evaluation of the immune cell subtypes and cytokines in the pericysts and surrounding liver and the antigen B (AgB)-specific response analysis of whole blood were performed. Results: In CE, the pericyst and the surrounding liver parenchyma showed aggregates of CD3+ T lymphocytes, mainly CD4+. B lymphocyte aggregates were present in the liver tissue. Monocytes/granulocytes were rarely observed. Th2 cytokine expression was scarce, whereas IFN-γ expression was present in the CE tissues. The control subject did not show an inflammatory infiltrate. The IL-4-specific response to AgB was increased in the patients with CE compared to the control, and this result was confirmed in a larger cohort (p = 0.003), whereas the IFN-γ-response was similar between the two groups (p = 0.5570). Conclusion: In patients with CE, CD4+ lymphocytes infiltrate the pericyst and the surrounding liver tissue with a low IL-4/IL-13 expression level and a moderate IFN-γ expression level; moreover, an IL-4 parasite-specific response is detected in the periphery. These results support adventitia involvement in CE immunopathogenesis.
Full article
(This article belongs to the Special Issue Zoonotic Cestodiasis: Echinococcosis and Taeniasis)
Open AccessArticle
The Phylogenetic Characterization of Balantioides coli Isolated in the Pavlova Culture Medium Supplemented with Coconut Water and Animal Serum
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Camila Souza Carvalho Class, Laís Lisboa Corrêa, Fabiana Batalha Knackfuss, Maria Regina Reis Amendoeira, Francisco Ponce Gordo and Alynne da Silva Barbosa
Pathogens 2024, 13(6), 476; https://doi.org/10.3390/pathogens13060476 - 4 Jun 2024
Abstract
Balantioides coli is a ciliated protist that can cause dysentery in humans, pigs and nonhuman primates and may have the potential for zoonotic transmission. Its diagnosis is routinely performed through conventional parasitological techniques, and few studies have used culturing techniques to isolate it,
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Balantioides coli is a ciliated protist that can cause dysentery in humans, pigs and nonhuman primates and may have the potential for zoonotic transmission. Its diagnosis is routinely performed through conventional parasitological techniques, and few studies have used culturing techniques to isolate it, applying molecular tools for the characterization of this protozoan. Thus, the objective of this study was to confirm B. coli diagnosis using molecular tools and to characterize the genetic variants of this parasite isolated from pigs kept on family farms in Brazil using three different culture media that differed in the serum added. Fecal samples from pigs were inoculated in Pavlova medium plus coconut water (PC), fetal bovine serum (PB) and horse serum (PH). Of the 127 samples positive for forms compatible with the phylum Ciliophora, 31 were selected for isolation. The most successful medium for isolation was PB 19/31 (61.3%), followed by PH 18/31 (58.1%) and PC 11/31 (35.5%). Of the nucleotide sequences generated, 20 were classified as genetic variant type B0, two as A1 and 15 as A0. The results indicated that PC, despite having allowed the isolation of B. coli for a short period, was not an adequate medium for the maintenance of this parasite in vitro, therefore requiring improvement.
Full article
(This article belongs to the Special Issue Prevalence, Pathology, and Alternative Control of Intestinal Parasites)
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Assessing the Prevalence and Dynamics of Emerging Campylobacterales in Human Stool Samples in Brussels by Filtration Culture
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Emmanuelle Giraudon, V. Y. Miendje Deyi and Delphine Martiny
Pathogens 2024, 13(6), 475; https://doi.org/10.3390/pathogens13060475 - 4 Jun 2024
Abstract
Thermophilic C. jejuni/coli is reported to be the first bacterial cause of gastroenteritis worldwide and the most common zoonosis in Europe. Although non-jejuni/coli Campylobacter sp. are increasingly suspected to be responsible for diarrhoea or to be involved in
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Thermophilic C. jejuni/coli is reported to be the first bacterial cause of gastroenteritis worldwide and the most common zoonosis in Europe. Although non-jejuni/coli Campylobacter sp. are increasingly suspected to be responsible for diarrhoea or to be involved in inflammatory bowel disease, they remain poorly isolated due to their fastidious and non-thermophilic nature. Additionally, they are not targeted by commercial syndromic PCR assays. In this study, we present routine diagnostic results over 6 years (2017–2019 and 2021–2023) of Campylobacter sp. and related species, obtained by optimised culture from 51,065 stools by both 0.65 µm pore filtration on antibiotic-free agar, incubated in an H2-enriched atmosphere at 37 °C (also known as the Cape Town protocol), and the use of selective inhibitory Butzler medium incubated at 42 °C. This allowed the isolation of 16 Campylobacter species, 2 Aliarcobacter species, and 2 Helicobacter species, providing a completely different view of the epidemiology of Campylobacterales, in which C. jejuni/coli represents only 30.0% of all isolates, while C. concisus represents 44.4%. C. ureolyticus, representing only 5.5% of all Campylobacterales pre-COVID-19, represented 20.6% of all strains post-COVID-19 (218% increase; p < 0.05). At the same time, the proportions of C. jejuni, C. coli, and C. concisus decreased by 37, 53, and 28%, respectively (p < 0.05).
Full article
(This article belongs to the Collection Campylobacter Infections Collection)
Open AccessArticle
The Anti-Inflammatory Effect of SDF-1 Derived Peptide on Porphyromonas gingivalis Infection via Regulation of NLRP3 and AIM2 Inflammasome
by
Si Yeong Kim, Min Kee Son, Jung Hwa Park, Hee Sam Na and Jin Chung
Pathogens 2024, 13(6), 474; https://doi.org/10.3390/pathogens13060474 - 4 Jun 2024
Abstract
(1) Background: Peptides are appealing as pharmacological materials because they are easily produced, safe, and tolerable. Despite increasing gum-care awareness, periodontitis is still prevalent and is influenced by factors like high sugar consumption, smoking, and aging. Porphyromonas gingivalis is considered a major
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(1) Background: Peptides are appealing as pharmacological materials because they are easily produced, safe, and tolerable. Despite increasing gum-care awareness, periodontitis is still prevalent and is influenced by factors like high sugar consumption, smoking, and aging. Porphyromonas gingivalis is considered a major etiologic agent of periodontitis and activates the NLR family pyrin domain containing 3 (NLRP3) but is absent in melanoma 2 (AIM2) inflammasomes, resulting in pro-inflammatory cytokine release. (2) Methods: We examined the anti-inflammatory effects of 18 peptides derived from human stromal cell-derived factor-1 (SDF-1) on THP-1 macrophages. Inflammation was induced by P. gingivalis, and the anti-inflammatory effects were analyzed using molecular biological techniques. In a mouse periodontitis model, alveolar bone resorption was assessed using micro-CT. (3) Results: Of the 18 SDF-1-derived peptides, S10 notably reduced IL-1β and TNF-α secretion. S10 also diminished the P. gingivalis-induced expression of NLRP3, AIM2, ASC (apoptosis-associated speck-like protein), caspase-1, and IL-1β. Furthermore, S10 attenuated the enhanced TLR (toll-like receptor) signaling pathway and decreased the phosphorylation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs). In addition, S10 mitigated alveolar bone loss in our P. gingivalis-induced mouse model of periodontitis. (4) Conclusions: S10 suppressed TLR/NF-κB/NLRP3 inflammasome signaling and the AIM2 inflammasome in our P. gingivalis-induced murine periodontitis model, which suggests that it has potential use as a therapeutic treatment for periodontitis.
Full article
(This article belongs to the Special Issue Nosocomial Infection and Antimicrobial Resistance)
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Evaluation of Immune Exhaustion and Co-Inhibitory Receptor Expression in Mycobacterium avium Subspecies paratuberculosis (MAP) Seropositive Diarrhoeic Bovines
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Shalini Sharma, Khushbu Sharma, Ram Kumar, Deen Dayal, Shweta Dhanda, Naveen Kumar, Kundan Kumar Chaubey, Shoor Vir Singh, Sikander Banger and Vishal Sharma
Pathogens 2024, 13(6), 473; https://doi.org/10.3390/pathogens13060473 - 4 Jun 2024
Abstract
Mycobacterium avium subspecies paratuberculosis (MAP) infection leads to chronic, persistent granulomatous enteritis, causing prolonged diarrhoea and emaciation. The disease is managed using medications such as antibiotics, live vaccines, mycobacteriophage therapies and other treatments; however, a notable proportion of affected animals do not show
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Mycobacterium avium subspecies paratuberculosis (MAP) infection leads to chronic, persistent granulomatous enteritis, causing prolonged diarrhoea and emaciation. The disease is managed using medications such as antibiotics, live vaccines, mycobacteriophage therapies and other treatments; however, a notable proportion of affected animals do not show improvement with this approach. We hypothesise that immunoinhibitory receptors TIM-3 (T cell immunoglobulin mucin protein-3) and PD-1 (Programmed death receptor 1) may be upregulated on Peripheral blood mononuclear cells (PBMCs) of MAP-seropositive bovines, potentially contributing to immune exhaustion. Samples (blood and faeces) were collected from 32 diarrhoeic bovines suspected of MAP infection; eight apparently healthy buffaloes from the dairy farm at Hisar, Haryana and from 14 cows (suffering from chronic diarrhoea, weakness and emaciation) housed in stray cattle shed. MAP infection was estimated using indigenous ELISA (i-ELISA), faecal IS900 PCR, culture and acid-fast staining. TIM-3 and PD-1 gene expression on PBMCs were determined using qRT-PCR. TIM3 expression was relatively higher (~400-fold, 330-fold, 112-fold, 65-fold and 16-fold) in 5 chronically diarrhoeic PBMCs samples (MAP-seropositive), and higher PD-1 expression (around ~7-fold, 1.75-fold, 2.5-fold, 7.6-fold) was recorded in 4 diarrhoeic MAP-seropositive animals, compared to apparently healthy and other MAP-seronegative diarrhoeic animals. High co-expression of TIM-3 and PD-1 levels was also recorded in chronically diarrhoeic, emaciated stray cattle. Understanding immune responses in field conditions might aid in the therapeutic management of paratuberculosis.
Full article
(This article belongs to the Special Issue T Cell Responses to Pathogenic Infections)
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Open AccessReview
The Role of the Airway and Gut Microbiome in the Development of Chronic Lung Disease of Prematurity
by
Lieve Boel, David J. Gallacher, Julian R. Marchesi and Sailesh Kotecha
Pathogens 2024, 13(6), 472; https://doi.org/10.3390/pathogens13060472 - 4 Jun 2024
Abstract
Chronic lung disease (CLD) of prematurity, a common cause of morbidity and mortality in preterm-born infants, has a multifactorial aetiology. This review summarizes the current evidence for the effect of the gut and airway microbiota on the development of CLD, highlighting the differences
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Chronic lung disease (CLD) of prematurity, a common cause of morbidity and mortality in preterm-born infants, has a multifactorial aetiology. This review summarizes the current evidence for the effect of the gut and airway microbiota on the development of CLD, highlighting the differences in the early colonisation patterns in preterm-born infants compared to term-born infants. Stool samples from preterm-born infants who develop CLD have less diversity than those who do not develop CLD. Pulmonary inflammation, which is a hallmark in the development of CLD, may potentially be influenced by gut bacteria. The respiratory microbiota is less abundant than the stool microbiota in preterm-born infants. There is a lack of clear evidence for the role of the respiratory microbiota in the development of CLD, with results from individual studies not replicated. A common finding is the presence of a single predominant bacterial genus in the lungs of preterm-born infants who develop CLD. Probiotic preparations have been proposed as a potential therapeutic strategy to modify the gut or lung microbiota with the aim of reducing rates of CLD but additional robust evidence is required before this treatment is introduced into routine clinical practice.
Full article
(This article belongs to the Special Issue Host-Pathogen Interaction in Respiratory Infections of the Neonate)
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Open AccessArticle
The Impact of Acute EBV Infection on Changes in the Serum Proteome in Children—A Pilot Study
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Katarzyna Mazur-Melewska, Magdalena Luczak, Joanna Watral, Paweł Małecki, Anna Mania and Magdalena Figlerowicz
Pathogens 2024, 13(6), 471; https://doi.org/10.3390/pathogens13060471 - 4 Jun 2024
Abstract
This study investigates the impact of Epstein–Barr virus (EBV) infection on children’s proteomes across different phases of the disease, utilising seventy-nine blood samples categorised into three groups: EBV-naive patients, acute infectious mononucleosis (IM) cases, and convalescents followed up for 12 months post-IM. The
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This study investigates the impact of Epstein–Barr virus (EBV) infection on children’s proteomes across different phases of the disease, utilising seventy-nine blood samples categorised into three groups: EBV-naive patients, acute infectious mononucleosis (IM) cases, and convalescents followed up for 12 months post-IM. The aim is to identify proteins influenced by EBV infection, shedding light on the chronic processes triggered by the virus. The results reveal thirty-nine proteins distinguishing between naive patients and those with IM, including actin, lumican, peroxiredoxin-2, fibulin-1, gelsolin, and alpha-2-macroglobulin, which are involved in immune responses, cell adhesion, and inflammation. Elevated oxidative stress markers like peroxiredoxin-2 in IM patients suggest potential links to EBV’s induction of reactive oxygen species. Increased levels of apolipoproteins A-I, A-IV, C-IV, and M during IM imply associations with viral infection, while complement system proteins (C1q, C1r, and C8 gamma chain) are also elevated, reflecting their role in the immune response and viral clearance. This study’s focus on children provides unique insights into EBV’s impact on young populations, emphasising proteomics’ role in uncovering protein associations and understanding the virus’s long-term consequences. However, specific relationships between identified proteins and EBV infection require further investigation.
Full article
(This article belongs to the Special Issue The Impact of Epstein Barr Virus (EBV) in Clinical Practice)
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Open AccessSystematic Review
Human Placental Schistosomiasis—A Systematic Review of the Literature
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Jacob Gerstenberg, Sasmita Mishra, Martha Holtfreter, Joachim Richter, Saskia Dede Davi, Dearie Glory Okwu, Michael Ramharter, Johannes Mischlinger and Benjamin T. Schleenvoigt
Pathogens 2024, 13(6), 470; https://doi.org/10.3390/pathogens13060470 - 3 Jun 2024
Abstract
Background: Schistosome egg deposition in pregnant women may affect the placenta of infected mothers and cause placental schistosomiasis (PS). Histopathological examination of placental tissue is an inadequate detection method due to low sensitivity. So far, there has not been any systematic review on
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Background: Schistosome egg deposition in pregnant women may affect the placenta of infected mothers and cause placental schistosomiasis (PS). Histopathological examination of placental tissue is an inadequate detection method due to low sensitivity. So far, there has not been any systematic review on PS. Methods: We conducted a systematic literature search on PubMed, EMBASE, and Medline and included all publications that reported microscopically confirmed cases of PS, as well as the relevant secondary literature found in the citations of the primarily included publications. Results: Out of 113 abstracts screened we found a total of 8 publications describing PS with a total of 92 cases describing egg deposition of dead and/or viable eggs and worms of S. haematobium and S. mansoni in placental tissue. One cross-sectional study investigating the prevalence of PS and its association with adverse birth outcomes, found 22% of placentas to be infested using a maceration technique but only <1% using histologic examination. Additionally, no direct link to deleterious pregnancy outcomes could be shown. Conclusions: PS is a highly unattended and underdiagnosed condition in endemic populations, due to a lack of awareness as well as low sensitivity of histopathological examinations. However, PS may play an important role in mediating or reinforcing adverse birth outcomes (ABO) such as fetal growth restriction (FGR) in maternal schistosomiasis, possibly by placental inflammation.
Full article
(This article belongs to the Special Issue Schistosomiasis: From Immunopathology to Vaccines)
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Open AccessArticle
Oropouche Virus Exposure in Febrile Patients during Chikungunya Virus Introduction in the State of Amapá, Amazon Region, Brazil
by
Raquel Curtinhas de Lima, Helver Gonçalves Dias, Thiara Manuele Alves de Souza, Débora Familiar-Macedo, Edcelha D’Athaide Ribeiro, Valmir Corrêa e Corrêa, Alex Pauvolid-Corrêa, Elzinandes Leal de Azeredo and Flávia Barreto dos Santos
Pathogens 2024, 13(6), 469; https://doi.org/10.3390/pathogens13060469 - 3 Jun 2024
Abstract
Oropouche orthobunyavirus (OROV) is an arbovirus transmitted by midges that has been involved in outbreaks throughout Central and South America. In Brazil, human cases have been historically concentrated in the northern region of the country. Oropouche fever in humans range from mild clinical
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Oropouche orthobunyavirus (OROV) is an arbovirus transmitted by midges that has been involved in outbreaks throughout Central and South America. In Brazil, human cases have been historically concentrated in the northern region of the country. Oropouche fever in humans range from mild clinical signs to rare neurological events, and is considered a neglected tropical disease in Brazil. Due to the clinical similarities to other arboviruses, such as chikungunya and dengue viruses, OROV infections are likely to be underreported. Chikungunya virus (CHIKV) cases in Brazil were first recognized in 2014 in the states of Amapá and Bahia in the north and northeast regions, respectively. Both OROV and CHIKV cause nonspecific symptoms, making clinical diagnosis difficult in a scenario of arbovirus cocirculation. Aiming to investigate OROV transmission during the CHIKV introduction in the state of Amapá located in the Brazilian Amazon, we conducted a retrospective molecular (RT-qPCR) and serological investigation in febrile cases (N = 166) collected between August 2014 and May 2015. All acute serum samples were negative for OROV RNA using RT-qPCR. However, neutralizing antibodies for OROV were detected using a plaque reduction neutralization test (PRNT90) in 10.24% (17/166) of the patients, with neutralizing antibody titers ranging from 20 to ≥640, suggesting the previous exposure of patients to OROV. Regarding CHIKV, recent exposure was confirmed by the detection of CHIKV RNA in 20.25% (33/163) of the patients and by the detection of anti-CHIKV IgM in 28.57% (44/154) of the patients. The additional detection of anti-CHIKV IgG in 12.58% (19/151) of the febrile patients suggests that some individuals had been previously exposed to CHIKV. Whether the OROV exposure reported here occurred prior or during the CHIKV circulation in Amapá, is unknown, but because those arboviral infections share similar clinical signs and symptoms, a silent circulation of enzootic arboviruses during the introduction of exotic arboviruses may occur, and highlights the importance of syndromic cases’ surveillance to arboviruses in Brazil.
Full article
(This article belongs to the Special Issue Emerging Arboviruses: Epidemiology, Vector Dynamics, and Pathogenesis)
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Open AccessArticle
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
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
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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.
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(This article belongs to the Special Issue Immunity to Respiratory Infections)
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Open AccessReview
Pediatric Tuberculosis: A Review of Evidence-Based Best Practices for Clinicians and Health Care Providers
by
Brittany K. Moore, Stephen M. Graham, Subhadra Nandakumar, Joshua Doyle and Susan A. Maloney
Pathogens 2024, 13(6), 467; https://doi.org/10.3390/pathogens13060467 - 1 Jun 2024
Abstract
Advances in pediatric TB care are promising, the result of decades of advocacy, operational and clinical trials research, and political will by national and local TB programs in high-burden countries. However, implementation challenges remain in linking policy to practice and scaling up innovations
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Advances in pediatric TB care are promising, the result of decades of advocacy, operational and clinical trials research, and political will by national and local TB programs in high-burden countries. However, implementation challenges remain in linking policy to practice and scaling up innovations for prevention, diagnosis, and treatment of TB in children, especially in resource-limited settings. There is both need and opportunity to strengthen clinician confidence in making a TB diagnosis and managing the various manifestations of TB in children, which can facilitate the translation of evidence to action and expand access to new tools and strategies to address TB in this population. This review aims to summarize existing guidance and best practices for clinicians and health care providers in low-resource, TB-endemic settings and identify resources with more detailed and actionable information for decision-making along the clinical cascade to prevent, find, and cure TB in children.
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(This article belongs to the Special Issue Recent Advances in Pediatric Infectious Diseases)
Open AccessArticle
Investigation of SARS-CoV-2 Infection among Companion Animals in Households with Confirmed Human COVID-19 Cases
by
Heather Venkat, Hayley D. Yaglom, Gavriella Hecht, Andrew Goedderz, Jennifer L. Ely, Michael Sprenkle, Taylor Martins, Daniel Jasso-Selles, Darrin Lemmer, Jordan Gesimondo, Irene Ruberto, Kenneth Komatsu and David M. Engelthaler
Pathogens 2024, 13(6), 466; https://doi.org/10.3390/pathogens13060466 - 1 Jun 2024
Abstract
We aimed to characterize SARS-CoV-2 infection in companion animals living in households with COVID-19-positive people and understand the dynamics surrounding how these animals become infected. Public health investigators contacted households with at least one confirmed, symptomatic person with COVID-19 for study recruitment. Blood,
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We aimed to characterize SARS-CoV-2 infection in companion animals living in households with COVID-19-positive people and understand the dynamics surrounding how these animals become infected. Public health investigators contacted households with at least one confirmed, symptomatic person with COVID-19 for study recruitment. Blood, nasal, and rectal swab specimens were collected from pet dogs and cats and a questionnaire was completed. Specimens were tested for SARS-CoV-2 by RT-PCR, and for neutralizing antibodies; genomic sequencing was performed on viral-positive samples. A total of 36.4% of 110 pets enrolled had evidence of infection with SARS-CoV-2. Pets were more likely to test positive if the pet was immunocompromised, and if more than one person in the home was positive for COVID-19. Among 12 multi-pet households where at least one pet was positive, 10 had at least one other pet test positive. Whole-genome sequencing revealed the genomes of viral lineages circulating in the community during the time of sample collection. Our findings suggest a high likelihood of viral transmission in households with multiple pets and when pets had very close interactions with symptomatic humans. Further surveillance studies are needed to characterize how new variants impact animals and to understand opportunities for infection and spillover in susceptible species.
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(This article belongs to the Special Issue From Sporadic Cases of Bird Flu to Global Pandemic of SARS-CoV-2: The Science Behind and Battle against Zoonotic Viruses)
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Open AccessReview
Aeromonas dhakensis: A Zoonotic Bacterium of Increasing Importance in Aquaculture
by
Kerry L. Bartie and Andrew P. Desbois
Pathogens 2024, 13(6), 465; https://doi.org/10.3390/pathogens13060465 - 31 May 2024
Abstract
Aeromonas dhakensis is increasingly recognised to be an important pathogen responsible for disease losses in warm-water aquaculture and, similar to several other Aeromonas species, it can infect humans. Knowledge of A. dhakensis is accumulating, but this species remains relatively under-investigated compared to its
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Aeromonas dhakensis is increasingly recognised to be an important pathogen responsible for disease losses in warm-water aquaculture and, similar to several other Aeromonas species, it can infect humans. Knowledge of A. dhakensis is accumulating, but this species remains relatively under-investigated compared to its close relative, Aeromonas hydrophila. The significance of A. dhakensis may have been overlooked in disease events of aquatic animals due to issues with reliable identification. Critical to appreciating the importance of this pathogen is the application of dependable molecular tools that enable accurate identification and discrimination from A. hydrophila and other motile aeromonads. This review aims to synthesise the key literature on A. dhakensis, particularly with relevance to aquaculture, including knowledge of the bacterium derived from disease case studies in aquatic hosts. Identification methods and strain phylogeny are discussed, with accurate detection important for prompt diagnosis and for distinguishing strains with heightened virulence. Increasing evidence suggests that A. dhakensis may be more virulent than A. hydrophila and correct identification is required to determine the zoonotic risks posed, which includes concerns for antibiotic-resistant strains. This review provides an impetus to improve species identification in the future and screen strain collections of presumptive Aeromonas spp. retrospectively to reveal the true prevalence and impact of A. dhakensis in aquaculture, the environment, and healthcare settings.
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(This article belongs to the Section Bacterial Pathogens)
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Recombinant Bile Salt Hydrolase Enhances the Inhibition Efficiency of Taurodeoxycholic Acid against Clostridium perfringens Virulence
by
Tahrir Alenezi, Bilal Alrubaye, Ying Fu, Janashrit Shrestha, Samar Algehani, Hong Wang, Rohana Liyanage and Xiaolun Sun
Pathogens 2024, 13(6), 464; https://doi.org/10.3390/pathogens13060464 - 31 May 2024
Abstract
Clostridium perfringens is the main pathogen of chicken necrotic enteritis (NE) causing huge economic losses in the poultry industry. Although dietary secondary bile acid deoxycholic acid (DCA) reduced chicken NE, the accumulation of conjugated tauro-DCA (TDCA) raised concerns regarding DCA efficacy. In this
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Clostridium perfringens is the main pathogen of chicken necrotic enteritis (NE) causing huge economic losses in the poultry industry. Although dietary secondary bile acid deoxycholic acid (DCA) reduced chicken NE, the accumulation of conjugated tauro-DCA (TDCA) raised concerns regarding DCA efficacy. In this study, we aimed to deconjugate TDCA by bile salt hydrolase (BSH) to increase DCA efficacy against the NE pathogen C. perfringens. Assays were conducted to evaluate the inhibition of C. perfringens growth, hydrogen sulfide (H2S) production, and virulence gene expression by TDCA and DCA. BSH activity and sequence alignment were conducted to select the bsh gene for cloning. The bsh gene from Bifidobacterium longum was PCR-amplified and cloned into plasmids pET-28a (pET-BSH) and pDR111 (pDR-BSH) for expressing the BSH protein in E. coli BL21 and Bacillus subtilis 168 (B-sub-BSH), respectively. His-tag-purified BSH from BL21 cells was evaluated by SDS-PAGE, Coomassie blue staining, and a Western blot (WB) assays. Secretory BSH from B. subtilis was analyzed by a Dot-Blot. B-sub-BSH was evaluated for the inhibition of C. perfringens growth. C. perfringens growth reached 7.8 log10 CFU/mL after 24 h culture. C. perfringens growth was at 8 vs. 7.4, 7.8 vs. 2.6 and 6 vs. 0 log10 CFU/mL in 0.2, 0.5, and 1 mM TDCA vs. DCA, respectively. Compared to TDCA, DCA reduced C. perfringens H2S production and the virulence gene expression of asrA1, netB, colA, and virT. BSH activity was observed in Lactobacillus johnsonii and B. longum under anaerobe but not L. johnsonii under 10% CO2 air. After the sequence alignment of bsh from ten bacteria, bsh from B. longum was selected, cloned into pET-BSH, and sequenced at 951 bp. After pET-BSH was transformed in BL21, BSH expression was assessed around 35 kDa using Coomassie staining and verified for His-tag using WB. After the subcloned bsh and amylase signal peptide sequence was inserted into pDR-BSH, B. subtilis was transformed and named B-sub-BSH. The transformation was evaluated using PCR with B. subtilis around 3 kb and B-sub-BSH around 5 kb. Secretory BSH expressed from B-sub-BSH was determined for His-tag using Dot-Blot. Importantly, C. perfringens growth was reduced greater than 59% log10 CFU/mL in the B-sub-BSH media precultured with 1 vs. 0 mM TDCA. In conclusion, TDCA was less potent than DCA against C. perfringens virulence, and recombinant secretory BSH from B-sub-BSH reduced C. perfringens growth, suggesting a new potential intervention against the pathogen-induced chicken NE.
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(This article belongs to the Special Issue Modulation of Gut Microbiota and Pathogens by Biotics (Prebiotics, Probiotics, Postbiotics, Parabiotics, Synbiotics))
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Molecular Detection and Genetic Characterization of Feline Immunodeficiency Virus (FIV) in Seropositive Cats in Northern Italy
by
Andrea Balboni, Veronica Facile, Laura Gallina, Maria Chiara Sabetti, Francesco Dondi and Mara Battilani
Pathogens 2024, 13(6), 463; https://doi.org/10.3390/pathogens13060463 - 31 May 2024
Abstract
Feline immunodeficiency virus (FIV) is responsible for immunodeficiency syndrome in cats. Several viral subtypes have been identified, each with a variable geographical distribution. To date, the subtype B is known to be the genotype spread in Italy. In this study, the genetic diversity
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Feline immunodeficiency virus (FIV) is responsible for immunodeficiency syndrome in cats. Several viral subtypes have been identified, each with a variable geographical distribution. To date, the subtype B is known to be the genotype spread in Italy. In this study, the genetic diversity of FIV in northern Italy was assessed by detecting proviral DNA in the blood samples of 50 cats determined to be positive through an anti-FIV antibodies test. These cats were tested using six different PCR assays, and the identified viruses were sequenced and analyzed. Forty-eight cats were confirmed positive, and several FIV subtypes were characterized. As expected, the subtype B was the most commonly observed, and the subtype A was reported for the first time in Italy. Moreover, a new taxon possibly representing an additional FIV subtype was detected, and one virus belonging to subtype B potentially had a recombinant origin. The genetic variability between the FIV viruses that emerged in this study may lead to the potential diagnostic failure of single molecular tests. Therefore, a new diagnostic strategy, which adopts different molecular tests and sequencing, is recommended to monitor the evolution and spread of FIV.
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(This article belongs to the Section Viral Pathogens)
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