Pathogens

6 pages, 416 KB

Open AccessArticle

Cold Enrichment Methods for the Detection of Foodborne Yersiniosis: Friend or Foe?

by Yuwei Zhang and Stephen L. W. On

Pathogens 2022, 11(2), 278; https://doi.org/10.3390/pathogens11020278 - 21 Feb 2022

Cited by 4 | Viewed by 3816

Yersinia enterocolitica and Y. pseudotuberculosis are important causes of enteric illness worldwide. Rapid response to suspected foodborne outbreaks is hampered by the widespread use of cold enrichment methods that require incubation periods of 10–21 days. Although these species grow faster at elevated temperatures, [...] Read more.

Yersinia enterocolitica and Y. pseudotuberculosis are important causes of enteric illness worldwide. Rapid response to suspected foodborne outbreaks is hampered by the widespread use of cold enrichment methods that require incubation periods of 10–21 days. Although these species grow faster at elevated temperatures, part of the rationale for cold enrichment is that a key pathogenicity marker (pYV virulence plasmid) is said to be lost at elevated temperatures. Experimental data on this claim seems scarce. We previously described an approach involving an enrichment step at 37 °C for Yersinia detection, applied this approach to additional strains, and examined the presence of plasmids in reisolates, as well as those recovered in our original study. Plasmids were recovered from every reisolate examined; the presence of marker genes yadA and virF denoted the virulence plasmid in 10 of the 11 strains examined. Use of an enrichment step at 37 °C does not appear to promote loss of the pYV or other plasmids harboured by foodborne pathogenic Y. enterocolitica and Y. pseudotuberculosis; wider adoption of this approach may assist the development of more rapid detection methods. Full article

(This article belongs to the Special Issue Yersinia enterocolitica and Yersinia pseudotuberculosis—Zoonotic Pathogens of Relevance to Public Health)

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10 pages, 834 KB

Open AccessArticle

Comparative Performance of Recombinant GRA6, GRA7, and GRA14 for the Serodetection of T. gondii Infection and Analysis of IgG Subclasses in Human Sera from the Philippines

by Rochelle Haidee Ybañez and Yoshifumi Nishikawa

Pathogens 2022, 11(2), 277; https://doi.org/10.3390/pathogens11020277 - 21 Feb 2022

Cited by 5 | Viewed by 2674

Abstract

Highly specific and sensitive diagnostic methods are vital for the effective control and treatment of toxoplasmosis. Routine diagnosis is primarily serological because T. gondii infections stimulate persistently high IgG antibody responses. The sensitivity and specificity of methods are crucial factors for the proper [...] Read more.

Highly specific and sensitive diagnostic methods are vital for the effective control and treatment of toxoplasmosis. Routine diagnosis is primarily serological because T. gondii infections stimulate persistently high IgG antibody responses. The sensitivity and specificity of methods are crucial factors for the proper diagnosis of toxoplasmosis, primarily dependent on the antigens used in different assays. In the present study, we compared the serodiagnostic performances of three recombinant dense granule antigens, namely, the GRA6, GRA7, and GRA14, to detect IgG antibodies against T. gondii in human sera from the Philippines. Moreover, we evaluated the IgG1, IgG2, IgG3, and IgG4 responses against the different recombinant antigens, which has not been performed previously. Our results revealed that the TgGRA7 has consistently displayed superior diagnostic capability, while TgGRA6 can be a satisfactory alternative antigen among the GRA proteins. Furthermore, IgG1 is the predominant subclass stimulated by the different recombinant antigens. This study’s results provide options to researchers and manufacturers to choose recombinant antigens suitable for their purpose. Full article

(This article belongs to the Special Issue Sero-Epidemiology of Natural Infections and Vaccination)

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12 pages, 1458 KB

Open AccessArticle

Imaging Aspects of Hepatic Alveolar Echinococcosis: Retrospective Findings of a Surgical Center in Turkey

by Mecit Kantarci, Sonay Aydin, Suat Eren, Hayri Ogul and Okan Akhan

Pathogens 2022, 11(2), 276; https://doi.org/10.3390/pathogens11020276 - 20 Feb 2022

Cited by 10 | Viewed by 2993

Abstract

Radiologists should be aware of the findings of alveolar echinococcosis (AE) due to the diagnostic and management value of imaging. We are attempting to define the most common diagnostic imaging findings of liver AE, along with the prevalence and distribution of those findings. [...] Read more.

Radiologists should be aware of the findings of alveolar echinococcosis (AE) due to the diagnostic and management value of imaging. We are attempting to define the most common diagnostic imaging findings of liver AE, along with the prevalence and distribution of those findings. The patients’ US, CT, and MRI images were reviewed retrospectively. CT images were acquired with and without the administration of contrast medium. The MRI protocol includes T2-weighted images (WI), diffusion (WI), apparent diffusion coefficient (ADC) maps, and pre- and post-contrast T1WIs. The current study included 61 patients. The mean age of the population was 58.2 ± 9.6 years According to Kratzer’s categorization (US), 139 lesions (73.1%) were categorized as hailstorm. According to Graeter’s classification (CT), 139 (73.1%) lesions were type 1-diffuse infiltrating. The most frequent types were Kodama type 2 and 3 lesions (MRI) (42.6% and 48.7%, accordingly). P2N0M0 was the most frequent subtype. The current study defines the major, characteristic imaging findings of liver AE using US, CT, and MRI. Since US, CT, and MRI have all been utilized to diagnose AE, we believe that a multi-modality classification system is needed. The study’s findings may aid radiologists in accurately and timely diagnosing liver AE. Full article

(This article belongs to the Special Issue Alveolar Echinococcosis: Joining Hands to Tackle a Lethal Parasitosis)

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38 pages, 8702 KB

Open AccessReview

SARS-CoV-2 and Coronavirus Disease Mitigation: Treatment Options, Vaccinations and Variants

by Almu’atasim Khamees, Jamal Bani-Issa, Mazhar Salim Al Zoubi, Taqwa Qasem, Manal Issam AbuAlArjah, Sura Ahmad Alawadin, Khayry Al-Shami, Farah E. Hussein, Emad Hussein, Ibrahim H. Bashayreh, Murtaza M. Tambuwala, Mohannad Al-Saghir and Christopher T. Cornelison

Pathogens 2022, 11(2), 275; https://doi.org/10.3390/pathogens11020275 - 20 Feb 2022

Cited by 13 | Viewed by 6452

Abstract

COVID-19 is caused by a novel coronavirus (2019-nCoV), which was declared as a pandemic after it emerged in China 2019. A vast international effort has been conducted to prevent and treat COVID-19 due to its high transmissibility and severe morbidity and mortality rates, [...] Read more.

COVID-19 is caused by a novel coronavirus (2019-nCoV), which was declared as a pandemic after it emerged in China 2019. A vast international effort has been conducted to prevent and treat COVID-19 due to its high transmissibility and severe morbidity and mortality rates, particularly in individuals with chronic co-morbidities. In addition, polymorphic variants increased the need for proper vaccination to overcome the infectivity of new variants that are emerging across the globe. Many treatment options have been proposed and more than 25 vaccines are in various stages of development; however, the infection peaks are oscillating periodically, which raises a significant question about the effectiveness of the prevention measures and the persistence of this pandemic disease. In this review, we are exploring the most recent knowledge and advances in the treatment and vaccination options as well as the new emerging variants of 2019-nCoV and the possible mitigation of one of the most aggressive pandemics in the last centuries. Full article

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22 pages, 1016 KB

Open AccessEditor’s ChoiceReview

Adaptive Cellular Immunity against African Swine Fever Virus Infections

by Alexander Schäfer, Giulia Franzoni, Christopher L. Netherton, Luise Hartmann, Sandra Blome and Ulrike Blohm

Pathogens 2022, 11(2), 274; https://doi.org/10.3390/pathogens11020274 - 20 Feb 2022

Cited by 49 | Viewed by 8162

Abstract

African swine fever virus (ASFV) remains a threat to global pig populations. Infections with ASFV lead to a hemorrhagic disease with up to 100% lethality in Eurasian domestic and wild pigs. Although myeloid cells are the main target cells for ASFV, T cell [...] Read more.

African swine fever virus (ASFV) remains a threat to global pig populations. Infections with ASFV lead to a hemorrhagic disease with up to 100% lethality in Eurasian domestic and wild pigs. Although myeloid cells are the main target cells for ASFV, T cell responses are impacted by the infection as well. The complex responses remain not well understood, and, consequently, there is no commercially available vaccine. Here, we review the current knowledge about the induction of antiviral T cell responses by cells of the myeloid lineage, as well as T cell responses in infected animals, recent efforts in vaccine research, and T cell epitopes present in ASFV. Full article

(This article belongs to the Special Issue Innate and Adaptive Immunity against Porcine Viruses)

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21 pages, 383 KB

Open AccessReview

Major Biological Control Strategies for Plant Pathogens

by Manisha Arora Pandit, Jitendra Kumar, Saloni Gulati, Neeru Bhandari, Poonam Mehta, Roma Katyal, Charu Dogra Rawat, Vachaspati Mishra and Jasleen Kaur

Pathogens 2022, 11(2), 273; https://doi.org/10.3390/pathogens11020273 - 19 Feb 2022

Cited by 186 | Viewed by 15037

Abstract

Food security has become a major concern worldwide in recent years due to ever increasing population. Providing food for the growing billions without disturbing environmental balance is incessantly required in the current scenario. In view of this, sustainable modes of agricultural practices offer [...] Read more.

Food security has become a major concern worldwide in recent years due to ever increasing population. Providing food for the growing billions without disturbing environmental balance is incessantly required in the current scenario. In view of this, sustainable modes of agricultural practices offer better promise and hence are gaining prominence recently. Moreover, these methods have taken precedence currently over chemical-based methods of pest restriction and pathogen control. Adoption of Biological Control is one such crucial technique that is currently in the forefront. Over a period of time, various biocontrol strategies have been experimented with and some have exhibited great success and promise. This review highlights the different methods of plant-pathogen control, types of plant pathogens, their modus operandi and various biocontrol approaches employing a range of microorganisms and their byproducts. The study lays emphasis on the use of upcoming methodologies like microbiome management and engineering, phage cocktails, genetically modified biocontrol agents and microbial volatilome as available strategies to sustainable agricultural practices. More importantly, a critical analysis of the various methods enumerated in the paper indicates the need to amalgamate these techniques in order to improve the degree of biocontrol offered by them. Full article

(This article belongs to the Topic Fungal Diversity)

11 pages, 599 KB

Open AccessArticle

More Insights about the Efficacy of Copper Ion Treatment on Mycobacterium avium subsp. paratuberculosis (MAP): A Clue for the Observed Tolerance

by Carlos Tejeda, Pamela Steuer, Marcela Villegas, Angelica Reyes-Jara, Esperanza C. Iranzo, Reydoret Umaña and Miguel Salgado

Pathogens 2022, 11(2), 272; https://doi.org/10.3390/pathogens11020272 - 19 Feb 2022

Cited by 3 | Viewed by 2386

Abstract

Background: Scientific evidence is scarce for the antimicrobial effect of copper on bacteria characterized as more resistant. Using Mycobacterium avium subsp. paratuberculosis (MAP), a highly resistant microorganism, as a pathogen model, copper ion treatment has shown a significant bactericidal effect; however, the sustainability [...] Read more.

Background: Scientific evidence is scarce for the antimicrobial effect of copper on bacteria characterized as more resistant. Using Mycobacterium avium subsp. paratuberculosis (MAP), a highly resistant microorganism, as a pathogen model, copper ion treatment has shown a significant bactericidal effect; however, the sustainability of MAP against copper toxicity was also reported in several studies. Accordingly, the present study aimed to evaluate the impacts of copper on MAP. Methodology: This study considered physicochemical properties and copper concentration in a buffer since it could modulate MAP response during the application of copper treatment. Results: Despite the efficacy of copper ions in significantly reducing the MAP load in Phosphate Buffered Saline, some MAP cells were able to survive. The copper concentration generated by the copper ion treatment device increased significantly with increasing exposure times. MAP bacterial load decreased significantly when treated with copper ions as the exposure times increased. An increase in pH decreased oxygen consumption, and an increase in conductivity was reported after treatment application. Conclusions: Even with higher concentrations of copper, the efficacy of MAP control was not complete. The concentration of copper must be a key element in achieving control of highly resistant microorganisms. Full article

(This article belongs to the Special Issue Feature Papers of Vaccines and Therapeutic Developments)

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25 pages, 435 KB

Open AccessEditor’s ChoiceReview

Methods of Inactivation of Highly Pathogenic Viruses for Molecular, Serology or Vaccine Development Purposes

by Simon Elveborg, Vanessa M. Monteil and Ali Mirazimi

Pathogens 2022, 11(2), 271; https://doi.org/10.3390/pathogens11020271 - 19 Feb 2022

Cited by 71 | Viewed by 21035

Abstract

The handling of highly pathogenic viruses, whether for diagnostic or research purposes, often requires an inactivation step. This article reviews available inactivation techniques published in peer-reviewed journals and their benefits and limitations in relation to the intended application. The bulk of highly pathogenic [...] Read more.

The handling of highly pathogenic viruses, whether for diagnostic or research purposes, often requires an inactivation step. This article reviews available inactivation techniques published in peer-reviewed journals and their benefits and limitations in relation to the intended application. The bulk of highly pathogenic viruses are represented by enveloped RNA viruses belonging to the Togaviridae, Flaviviridae, Filoviridae, Arenaviridae, Hantaviridae, Peribunyaviridae, Phenuiviridae, Nairoviridae and Orthomyxoviridae families. Here, we summarize inactivation methods for these virus families that allow for subsequent molecular and serological analysis or vaccine development. The techniques identified here include: treatment with guanidium-based chaotropic salts, heat inactivation, photoactive compounds such as psoralens or 1.5-iodonaphtyl azide, detergents, fixing with aldehydes, UV-radiation, gamma irradiation, aromatic disulfides, beta-propiolacton and hydrogen peroxide. The combination of simple techniques such as heat or UV-radiation and detergents such as Tween-20, Triton X-100 or Sodium dodecyl sulfate are often sufficient for virus inactivation, but the efficiency may be affected by influencing factors including quantity of infectious particles, matrix constitution, pH, salt- and protein content. Residual infectivity of the inactivated virus could have disastrous consequences for both laboratory/healthcare personnel and patients. Therefore, the development of inactivation protocols requires careful considerations which we review here. Full article

(This article belongs to the Special Issue Highly Pathogenic Viruses: Challenges for Diagnostics Development and Drug Discovery)

9 pages, 235 KB

Open AccessHypothesis

Patients with Obesity and a History of Metformin Treatment Have Lower Influenza Mortality: A Retrospective Cohort Study

by Tammy H. Cummings, Joseph Magagnoli, James W. Hardin and S. Scott Sutton

Pathogens 2022, 11(2), 270; https://doi.org/10.3390/pathogens11020270 - 19 Feb 2022

Cited by 9 | Viewed by 3064

Abstract

Background: Obesity is a risk factor for the development of influenza by leading to a chronic inflammatory state and T-cell dysfunction. Based upon preclinical research, metformin has influenza activity by restoring T-cell function and improving the immune response. Objective: We aimed to evaluate [...] Read more.

Background: Obesity is a risk factor for the development of influenza by leading to a chronic inflammatory state and T-cell dysfunction. Based upon preclinical research, metformin has influenza activity by restoring T-cell function and improving the immune response. Objective: We aimed to evaluate the potential drug repurposing of metformin for the management of influenza among patients with obesity utilizing national claims data in an electronic health record database. Methods: The VA Informatics and Computing Infrastructure (VINCI) was utilized to obtain individual-level information on demographics, administrative claims, and pharmacy dispensation. A cohort was created among individuals with laboratory confirmed diagnosis of influenza with a diagnosis of fever, cough, influenza, or acute upper respiratory infection in an outpatient setting. The study outcome was death after diagnosis of influenza. Cohorts were formed using diabetes status and metformin exposure prior to a positive influenza diagnosis. Hazard ratios for mortality were estimated using a cox proportional hazards model adjusting for baseline covariates and a sub-analysis was conducted utilizing propensity score matching. A greedy nearest neighbor algorithm was utilized to match 1 to 1 non-metformin diabetic controls and non-diabetic controls to diabetic patients receiving metformin. Results: A total of 3551 patients met the inclusion criteria and were evaluated in our study. The cohorts consisted of 1461 patients in the non-diabetic cohort, 1597 patients in the diabetic / metformin cohort, and 493 patients in the diabetic no metformin cohort. Compared to non-diabetic patients, diabetic patients with metformin had a lower rate of death (aHR 0.78, 95% CI 0.609–0.999). There was not a statistical difference between the non-diabetic patients and the diabetic patients without metformin (aHR 1.046, 95% CI 0.781–1.400). The propensity score matched cohorts revealed consistent results with the primary analysis. Conclusion: Our results demonstrated patients with obesity and a history of metformin treatment have lower influenza mortality. Full article

(This article belongs to the Special Issue Fighting Flu—Recent Advances in Influenza Research)

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14 pages, 1624 KB

Open AccessEditor’s ChoiceSystematic Review

Long-Term Sequelae of COVID-19: A Systematic Review and Meta-Analysis of One-Year Follow-Up Studies on Post-COVID Symptoms

by Qing Han, Bang Zheng, Luke Daines and Aziz Sheikh

Pathogens 2022, 11(2), 269; https://doi.org/10.3390/pathogens11020269 - 19 Feb 2022

Cited by 438 | Viewed by 25840

Abstract

Emerging evidence has shown that COVID-19 survivors could suffer from persistent symptoms. However, it remains unclear whether these symptoms persist over the longer term. This study aimed to systematically synthesise evidence on post-COVID symptoms persisting for at least 12 months. We searched PubMed [...] Read more.

Emerging evidence has shown that COVID-19 survivors could suffer from persistent symptoms. However, it remains unclear whether these symptoms persist over the longer term. This study aimed to systematically synthesise evidence on post-COVID symptoms persisting for at least 12 months. We searched PubMed and Embase for papers reporting at least one-year follow-up results of COVID-19 survivors published by 6 November 2021. Random-effects meta-analyses were conducted to estimate pooled prevalence of specific post-COVID symptoms. Eighteen papers that reported one-year follow-up data from 8591 COVID-19 survivors were included. Fatigue/weakness (28%, 95% CI: 18–39), dyspnoea (18%, 95% CI: 13–24), arthromyalgia (26%, 95% CI: 8–44), depression (23%, 95% CI: 12–34), anxiety (22%, 95% CI: 15–29), memory loss (19%, 95% CI: 7–31), concentration difficulties (18%, 95% CI: 2–35), and insomnia (12%, 95% CI: 7–17) were the most prevalent symptoms at one-year follow-up. Existing evidence suggested that female patients and those with more severe initial illness were more likely to suffer from the sequelae after one year. This study demonstrated that a sizeable proportion of COVID-19 survivors still experience residual symptoms involving various body systems one year later. There is an urgent need for elucidating the pathophysiologic mechanisms and developing and testing targeted interventions for long-COVID patients. Full article

(This article belongs to the Special Issue Emerging and/or Zoonotic Viral Infections)

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10 pages, 1362 KB

Open AccessArticle

Metabolic Alteration of Trypanosoma cruzi during Differentiation of Epimastigote to Trypomastigote Forms

by Salvatore G. De-Simone, Saulo C. Bourguignon, Priscila S. Gonçalves, Guilherme C. Lechuga and David W. Provance, Jr.

Pathogens 2022, 11(2), 268; https://doi.org/10.3390/pathogens11020268 - 19 Feb 2022

Cited by 10 | Viewed by 3549

Abstract

Intracellular parasites such as Trypanosoma cruzi need to acquire valuable carbon sources from the host cell to replicate. Here, we investigated the energetic metabolism of T. cruzi during metacyclogenesis through the determination of enzymatic activities and quantification by HPLC of glycolytic and Krebs [...] Read more.

Intracellular parasites such as Trypanosoma cruzi need to acquire valuable carbon sources from the host cell to replicate. Here, we investigated the energetic metabolism of T. cruzi during metacyclogenesis through the determination of enzymatic activities and quantification by HPLC of glycolytic and Krebs cycle short-chain carboxylic acids. Altered concentrations in pyruvate, acetate, succinate, and glycerate were measured during the growth of epimastigote in the complex medium BHI and their differentiation to trypomastigotes in the chemically defined medium, TAU3AAG. These alterations should represent significant differential metabolic modifications utilized by either form to generate energy. This paper is the first work dealing with the intracellular organic acid concentration measurement in T. cruzi parasites. Although it confirms the previous assumption of the importance of carbohydrate metabolism, it yields an essential improvement in T. cruzi metabolism knowledge. Full article

(This article belongs to the Special Issue Metabolism for Parasitism)

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11 pages, 1489 KB

Open AccessArticle

Plant- and Bacteria-Derived Compounds with Anti-Philasterides dicentrarchi Activity

by Rosa Ana Sueiro, José Manuel Leiro, Verónica Blanco-Abad, Jos Raaijmakers, Irene de Bruijn, Ron P. H. Dirks and Jesús Lamas

Pathogens 2022, 11(2), 267; https://doi.org/10.3390/pathogens11020267 - 18 Feb 2022

Cited by 3 | Viewed by 2971

Abstract

Philasterides dicentrarchi is a scuticociliate that causes high mortalities in farmed fish. Although vaccination is an effective method to prevent scuticociliatosis caused by the homologous serotype, a universal vaccine has not been developed yet. Many compounds have been shown to be toxic to [...] Read more.

Philasterides dicentrarchi is a scuticociliate that causes high mortalities in farmed fish. Although vaccination is an effective method to prevent scuticociliatosis caused by the homologous serotype, a universal vaccine has not been developed yet. Many compounds have been shown to be toxic to this ciliate species; moreover, most of them are toxic to aquatic life and cannot be used to prevent the disease. We have evaluated the toxicity to P. dicentrarchi of several compounds of natural origin to be used to reduce parasite levels in the seawater. Ciliates were exposed to several compound concentrations, and the mortality was determined at several incubation times. Tomatine, plumbagin and 2′,4′-dihydroxychalcone displayed the highest anticiliate activity, with a dose-dependent response. The effects of these compounds on the EPC cell line were also evaluated, finding that 2′,4′-dihydroxychalcone displayed the lowest toxicity to fish cells. At 7.54 μM, 2′,4′-dihydroxychalcone inhibited 50% parasite growth but only killed about 10% of EPC cells after 24 h incubation. Finally, we evaluated the toxicity of Pseudomonas H6 surfactant (PS) to P. dicentrarchi, finding that PS was toxic to the ciliate but showed lower toxicity to EPC cells. At a concentration of 7.8 μg/mL (LC₅₀ for the ciliate after 3 h incubation), PS killed 14.9% of EPC cells. We conclude that 2′,4′-dihydroxychalcone, and PS could be used to reduce parasite levels in seawater, thus decreasing the risk of scuticociliatosis infection in cultured fish. Full article

(This article belongs to the Special Issue ParaFishControl: Advanced Tools and Research Strategies for Parasite Control in European Farmed Fish)

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20 pages, 6482 KB

Open AccessArticle

Tumor Cell Plasticity in Equine Papillomavirus-Positive Versus-Negative Squamous Cell Carcinoma of the Head and Neck

by Carina Strohmayer, Andrea Klang, Stefan Kummer, Ingrid Walter, Christoph Jindra, Christiane Weissenbacher-Lang, Torben Redmer, Sibylle Kneissl and Sabine Brandt

Pathogens 2022, 11(2), 266; https://doi.org/10.3390/pathogens11020266 - 18 Feb 2022

Cited by 10 | Viewed by 3014

Abstract

Squamous cell carcinoma of the head and neck (HNSCC) is a common malignant tumor in humans and animals. In humans, papillomavirus (PV)-induced HNSCCs have a better prognosis than papillomavirus-unrelated HNSCCs. The ability of tumor cells to switch from epithelial to mesenchymal, endothelial, or [...] Read more.

Squamous cell carcinoma of the head and neck (HNSCC) is a common malignant tumor in humans and animals. In humans, papillomavirus (PV)-induced HNSCCs have a better prognosis than papillomavirus-unrelated HNSCCs. The ability of tumor cells to switch from epithelial to mesenchymal, endothelial, or therapy-resistant stem-cell-like phenotypes promotes disease progression and metastasis. In equine HNSCC, PV-association and tumor cell phenotype switching are poorly understood. We screened 49 equine HNSCCs for equine PV (EcPV) type 2, 3 and 5 infection. Subsequently, PV-positive versus -negative lesions were analyzed for expression of selected epithelial (keratins, β-catenin), mesenchymal (vimentin), endothelial (COX-2), and stem-cell markers (CD271, CD44) by immunohistochemistry (IHC) and immunofluorescence (IF; keratins/vimentin, CD44/CD271 double-staining) to address tumor cell plasticity in relation to PV infection. Only EcPV2 PCR scored positive for 11/49 equine HNSCCs. IHC and IF from 11 EcPV2-positive and 11 EcPV2-negative tumors revealed epithelial-to-mesenchymal transition events, with vimentin-positive cells ranging between <10 and >50%. CD44- and CD271-staining disclosed the intralesional presence of infiltrative tumor cell fronts and double-positive tumor cell subsets independently of the PV infection status. Our findings are indicative of (partial) epithelial–mesenchymal transition events giving rise to hybrid epithelial/mesenchymal and stem-cell-like tumor cell phenotypes in equine HNSCCs and suggest CD44 and CD271 as potential malignancy markers that merit to be further explored in the horse. Full article

(This article belongs to the Special Issue Animal Papillomavirus: Virus Identification, Diagnosis and Co-infections)

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10 pages, 9259 KB

Open AccessFeature PaperArticle

Rabies Virus Variants Detected from Cougar (Puma concolor) in Mexico 2000–2021

by Fabiola Garcés-Ayala, Álvaro Aguilar-Setién, Cenia Almazán-Marín, Claudia Cuautle-Zavala, Susana Chávez-López, David Martínez-Solís, Mauricio Gómez-Sierra, Albert Sandoval-Borja, Beatriz Escamilla-Ríos, Irma López-Martínez and Nidia Aréchiga-Ceballos

Pathogens 2022, 11(2), 265; https://doi.org/10.3390/pathogens11020265 - 18 Feb 2022

Cited by 5 | Viewed by 3765

Abstract

In 2019, the World Health Organization (WHO) and the Pan-American Health Organization (PAHO) recognized Mexico as a country free of human rabies transmitted by dogs. Nevertheless, the sylvatic cycle remains as a public health concern in the country. Although cougars (Puma concolor [...] Read more.

In 2019, the World Health Organization (WHO) and the Pan-American Health Organization (PAHO) recognized Mexico as a country free of human rabies transmitted by dogs. Nevertheless, the sylvatic cycle remains as a public health concern in the country. Although cougars (Puma concolor) are not reservoirs of any rabies virus variant (RVV), these felines could act as vectors at the top of the food chain, and their relationships with other organisms must be considered important for the regulatory effect on their prey’s populations. In this study, genetic and antigenic characterization was performed on all cougar rabies cases diagnosed at the Rabies Laboratory Network of the Ministry of Health (RLNMH) in Mexico from 2000 to 2021. Samples from other species, a skunk, a horse (Equus caballus) (attacked by a cougar), and a gray fox (Urocyon cineroargenteus), were included as reference. Rabies cases in cougars were restricted to two Northern states of Mexico (Sonora and Chihuahua). Five out of six samples of cougars were RVV7 (Arizona gray fox RVV) and one from Sonora was RVV1. Interestingly, there is no evidence of RVV1 in dogs in the Northern states since the 1990s but skunk species now harbor this RVV1 in this region of the country. Full article

(This article belongs to the Special Issue Emerging and Endemic Infections in Wildlife: Epidemiology, Ecology, & Management in a Changing World)

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14 pages, 6110 KB

Open AccessArticle

Novel Quantitative Assay to Describe In Vitro Bovine Mastitis Bacterial Pathogen Inhibition by Non-aureus Staphylococci

by Bruno Toledo-Silva, Lisa Beuckelaere, Anneleen De Visscher, Chloë Geeroms, Evelyne Meyer, Sofie Piepers, Damien Thiry, Freddy Haesebrouck and Sarne De Vliegher

Pathogens 2022, 11(2), 264; https://doi.org/10.3390/pathogens11020264 - 18 Feb 2022

Cited by 8 | Viewed by 2869

Abstract

In this paper, we describe a new quantitative method to evaluate and quantify in vitro growth inhibition of mastitis-related bacteria. Colony-forming units of Staphylococcus (S.) aureus (n = 10), Escherichia (E.) coli (n = 10), and Streptococcus (S.) uberis (n [...] Read more.

In this paper, we describe a new quantitative method to evaluate and quantify in vitro growth inhibition of mastitis-related bacteria. Colony-forming units of Staphylococcus (S.) aureus (n = 10), Escherichia (E.) coli (n = 10), and Streptococcus (S.) uberis (n = 10) were quantified after their growth on top of layers of trypticase soy agar (TSA) containing six different concentrations (varying from 10² to 10⁷ CFU/mL) of bovine non-aureus staphylococci (NAS), i.e., S. chromogenes (n = 3) and S. simulans (n = 3) isolates. Growth inhibition of the mastitis-related major bacterial pathogens, including E. coli, was confirmed by all NAS, an effect that varied highly among NAS isolates and was not evident from the semiquantitative method with which the new method was compared. By subsequent application of the new method on a larger set of 14 bovine NAS isolates, we observed that S. simulans and NAS originating from teat apices (especially S. epidermidis) required lower concentrations to inhibit both methicillin-sensitive (MSSA) (n = 5) and methicillin-resistant S. aureus (MRSA) isolates (n = 5) originating from milk. Therefore, the new assay is a promising tool to precisely quantify the intra- and inter-species differences in growth inhibition between NAS. Full article

(This article belongs to the Special Issue Bacteria Involved in Ruminant Mastitis)

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3 pages, 223 KB

Open AccessComment

Call for Caution to Consider Babesia bovis and Babesia bigemina as Anthropozoonotic Agents in Colombia. Comment on Kumar et al. The Global Emergence of Human Babesiosis. Pathogens 2021, 10, 1447

by Carlos Ramiro Silva-Ramos and Álvaro A. Faccini-Martínez

Pathogens 2022, 11(2), 263; https://doi.org/10.3390/pathogens11020263 - 18 Feb 2022

Cited by 4 | Viewed by 2495

Abstract

Currently, six species and two genetic variants within Babesia genus have been confirmed as human pathogens. Babesia bovis and Babesia bigemina are causative agents of bovine babesiosis, and, in spite of the worldwide distribution of those species and their vectors, no description of [...] Read more.

Currently, six species and two genetic variants within Babesia genus have been confirmed as human pathogens. Babesia bovis and Babesia bigemina are causative agents of bovine babesiosis, and, in spite of the worldwide distribution of those species and their vectors, no description of related human cases has been reported. As a contribution, we would like to address the articles which claim the alleged role of B. bovis and B. bigemina as anthropozoonotic pathogens in Colombia. Full article

(This article belongs to the Special Issue Babesia and Human Babesiosis)

9 pages, 7929 KB

Open AccessArticle

An Experimental Evaluation of Toxicity Effects of Sodium Chloride on Oviposition, Hatching and Larval Development of Aedes albopictus

by Xiang Guo, Siyun Zhou, Jing Wu, Xiaoqing Zhang, Yuji Wang, Zixuan Li, Xiao-Guang Chen and Xiaohong Zhou

Pathogens 2022, 11(2), 262; https://doi.org/10.3390/pathogens11020262 - 18 Feb 2022

Cited by 3 | Viewed by 2914

Abstract

Dengue virus, one of the most important mosquito-borne viruses, has shown a sharp upward trend, spreading around the world in recent years. Control of vectors Aedes aegypti and Ae. albopictus remains crucial for blocking dengue transmission. The lethal ovitrap (LO) is one of [...] Read more.

Dengue virus, one of the most important mosquito-borne viruses, has shown a sharp upward trend, spreading around the world in recent years. Control of vectors Aedes aegypti and Ae. albopictus remains crucial for blocking dengue transmission. The lethal ovitrap (LO) is one of the cost-effective traps based on the classic “lure and kill” strategy, and finding a proper long-lasting effective toxin is key to achieving the desired effect. The concentration of inorganic salts of habitat environment plays a strong role in affecting oviposition, hatching, and development of mosquitoes, but the potential insecticide activity of Sodium Chloride (NaCl) in habitat water as well as LO still lacks research. In this study, we carried out laboratory experiments to systematically explore the effects of different concentrations of NaCl solutions on oviposition, egg hatching, and larval development of Ae. albopictus. Consequently, Ae. albopictus was found to prefer freshwater to lay eggs; whereas 48.8 ± 2.6% eggs were laid in freshwater and 20% in ≥1.0% brackish water, few eggs were laid in 3.0% NaCl solution. Compared with egg hatching, larval development of Ae. albopictus presented a higher sensibility to NaCl concentration. The mortality of the 3rd–4th larvae in 1.0% NaCl solution was 83.8 ± 8.7%, while in 3.0% it reached 100%. Considering the cumulative effect of NaCl, when NaCl concentration was ≥1.0%, no eggs could successfully develop into adults. These data suggested that NaCl solutions with a concentration ≥1.0% can be used as an effective cheap insecticide for Ae. albopictus in subtropical inland aquatic habitats, and also as the “kill” toxin in LOs. Meanwhile, the concentration range from 0 to 2.0% of NaCl solution has the potential to be used as the “lure” in LOs. The technological processes of how to use NaCl as insecticide or in LOs still needs further in-depth exploration. Full article

(This article belongs to the Special Issue Mosquito-Borne Diseases: Novel Control Strategies)

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9 pages, 531 KB

Open AccessArticle

Evaluation of Eosinophilic Cationic Protein as a Marker of Alveolar and Cystic Echinococcosis

by Julian Frederic Hotz, Klaus Kaczirek, Stefan Stremitzer, Fredrik Waneck, Herbert Auer, Thomas Perkmann, Manuel Kussmann, Philipp Karl Bauer, Rui-Yang Chen, Richard Kriz, Heinz Burgmann, Michael Ramharter and Heimo Lagler

Pathogens 2022, 11(2), 261; https://doi.org/10.3390/pathogens11020261 - 18 Feb 2022

Cited by 4 | Viewed by 2713

Abstract

Echinococcosis is a neglected zoonotic disease and a worldwide public health problem caused by infection with the larval stages of taeniid cestodes of the genus Echinococcus. In vitro studies have demonstrated a protoscolecidal effect of eosinophilic cationic protein (ECP), a granule protein [...] Read more.

Echinococcosis is a neglected zoonotic disease and a worldwide public health problem caused by infection with the larval stages of taeniid cestodes of the genus Echinococcus. In vitro studies have demonstrated a protoscolecidal effect of eosinophilic cationic protein (ECP), a granule protein of eosinophilic granulocytes, against E. granulosus. Therefore, the main objective of this study was to evaluate ECP as a biomarker in the treatment of alveolar echinococcosis (AE) and cystic echinococcosis (CE). Data were collected retrospectively from the Vienna Echinococcosis Cohort over 7 years until December 2020. Altogether, 32 patients (16 AE and 16 CE) were included. In the selected patients, serum ECP values were compared before and after the beginning of an operative and/or benzimidazole (BMZ) therapy. Mean ECP serum levels before intervention were significantly (p < 0.05) elevated at 34.0 ± 22.9 μg/L in AE patients and at 38.6 ± 19.9 μg/L in CE patients compared to the control group. After the intervention, mean ECP levels decreased significantly (p < 0.05) to 20.4 ± 14.6 μg/L in AE patients and to 22.4 ± 8.3 μg/L in CE patients. Furthermore, ECP showed a significant (p < 0.05) correlation of k = 0.56 with PET–CTI. Based on the significant decrease after operative and/or BMZ treatment and the correlation with clinical markers such as PET–CTI, it is recommended to investigate ECP more intensively as a marker of AE and CE in prospective studies with larger cohorts. Full article

(This article belongs to the Special Issue Alveolar Echinococcosis: Joining Hands to Tackle a Lethal Parasitosis)

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11 pages, 1194 KB

Open AccessCommunication

Intra-Palpebral Tuberculin Skin Test and Interferon Gamma Release Assay in Diagnosing Tuberculosis Due to Mycobacterium caprae in European Bison (Bison bonasus)

by Anna Didkowska, Blanka Orłowska, Monika Krajewska-Wędzina, Michał Krzysiak, Małgorzata Bruczyńska, Jan Wiśniewski, Daniel Klich, Wanda Olech and Krzysztof Anusz

Pathogens 2022, 11(2), 260; https://doi.org/10.3390/pathogens11020260 - 17 Feb 2022

Cited by 10 | Viewed by 3075

Abstract

Despite the threat posed by tuberculosis (TB) to the protected European bison (Bison bonasus), no validated TB tests exist for this species. This pilot study evaluates two tests based on detecting cellular immunity for this purpose: interferon gamma release assay (IGRA) [...] Read more.

Despite the threat posed by tuberculosis (TB) to the protected European bison (Bison bonasus), no validated TB tests exist for this species. This pilot study evaluates two tests based on detecting cellular immunity for this purpose: interferon gamma release assay (IGRA) and tuberculin skin test (TST). Ten animals were subjected to ante-mortem and post-mortem examinations. IGRA was performed using a commercial test, and the comparative TST was performed in the eyelids. The lesions were assessed post-mortem and material was collected for mycobacterial culture. The isolated strains were subjected to genotyping. At post-mortem examination, five out of ten individuals demonstrated both tuberculous lesions and positive culture results (Mycobacterium caprae). Compared to the palpebral TST, the findings of the IGRA are easier to interpret when diagnosing tuberculosis in European bison. Full article

(This article belongs to the Special Issue Emerging and Endemic Infections in Wildlife: Epidemiology, Ecology, & Management in a Changing World)

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18 pages, 3964 KB

Open AccessArticle

Deciphering the Interactions of SARS-CoV-2 Proteins with Human Ion Channels Using Machine-Learning-Based Methods

by Nupur S. Munjal, Dikscha Sapra, K. T. Shreya Parthasarathi, Abhishek Goyal, Akhilesh Pandey, Manidipa Banerjee and Jyoti Sharma

Pathogens 2022, 11(2), 259; https://doi.org/10.3390/pathogens11020259 - 17 Feb 2022

Cited by 6 | Viewed by 3677

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is accountable for the protracted COVID-19 pandemic. Its high transmission rate and pathogenicity led to health emergencies and economic crisis. Recent studies pertaining to the understanding of the molecular pathogenesis of SARS-CoV-2 infection exhibited the indispensable [...] Read more.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is accountable for the protracted COVID-19 pandemic. Its high transmission rate and pathogenicity led to health emergencies and economic crisis. Recent studies pertaining to the understanding of the molecular pathogenesis of SARS-CoV-2 infection exhibited the indispensable role of ion channels in viral infection inside the host. Moreover, machine learning (ML)-based algorithms are providing a higher accuracy for host-SARS-CoV-2 protein–protein interactions (PPIs). In this study, PPIs of SARS-CoV-2 proteins with human ion channels (HICs) were trained on the PPI-MetaGO algorithm. PPI networks (PPINs) and a signaling pathway map of HICs with SARS-CoV-2 proteins were generated. Additionally, various U.S. food and drug administration (FDA)-approved drugs interacting with the potential HICs were identified. The PPIs were predicted with 82.71% accuracy, 84.09% precision, 84.09% sensitivity, 0.89 AUC-ROC, 65.17% Matthews correlation coefficient score (MCC) and 84.09% F1 score. Several host pathways were found to be altered, including calcium signaling and taste transduction pathway. Potential HICs could serve as an initial set to the experimentalists for further validation. The study also reinforces the drug repurposing approach for the development of host directed antiviral drugs that may provide a better therapeutic management strategy for infection caused by SARS-CoV-2. Full article

(This article belongs to the Special Issue Viral Pathogenesis and Immunity)

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14 pages, 1121 KB

Open AccessReview

Nematode Orthologs of Macrophage Migration Inhibitory Factor (MIF) as Modulators of the Host Immune Response and Potential Therapeutic Targets

by Justyna Karabowicz, Ewa Długosz, Piotr Bąska and Marcin Wiśniewski

Pathogens 2022, 11(2), 258; https://doi.org/10.3390/pathogens11020258 - 17 Feb 2022

Cited by 14 | Viewed by 4188

Abstract

One of the adaptations of nematodes, which allows long-term survival in the host, is the production of proteins with immunomodulatory properties. The parasites secrete numerous homologs of human immune mediators, such as macrophage migration inhibitory factor (MIF), which is a substantial regulator of [...] Read more.

One of the adaptations of nematodes, which allows long-term survival in the host, is the production of proteins with immunomodulatory properties. The parasites secrete numerous homologs of human immune mediators, such as macrophage migration inhibitory factor (MIF), which is a substantial regulator of the inflammatory immune response. Homologs of mammalian MIF have been recognized in many species of nematode parasites, but their role has not been fully understood. The application of molecular biology and genetic engineering methods, including the production of recombinant proteins, has enabled better characterization of their structure and properties. This review provides insight into the current state of knowledge on MIF homologs produced by nematodes, as well as their structure, enzymatic activity, tissue expression pattern, impact on the host immune system, and potential use in the treatment of parasitic, inflammatory, and autoimmune diseases. Full article

(This article belongs to the Special Issue Immune Response of the Host and Vaccine Development)

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12 pages, 1727 KB

Open AccessEditor’s ChoiceArticle

SARS-CoV-2 Infects Primary Neurons from Human ACE2 Expressing Mice and Upregulates Genes Involved in the Inflammatory and Necroptotic Pathways

by Hussin A. Rothan, Pratima Kumari, Shannon Stone, Janhavi P. Natekar, Komal Arora, Tabassum T. Auroni and Mukesh Kumar

Pathogens 2022, 11(2), 257; https://doi.org/10.3390/pathogens11020257 - 17 Feb 2022

Cited by 28 | Viewed by 5294

Abstract

Transgenic mice expressing human angiotensin-converting enzyme 2 under the cytokeratin 18 promoter (K18-hACE2) have been extensively used to investigate the pathogenesis and tissue tropism of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Neuroinvasion and the replication of SARS-CoV-2 within the central nervous system [...] Read more.

Transgenic mice expressing human angiotensin-converting enzyme 2 under the cytokeratin 18 promoter (K18-hACE2) have been extensively used to investigate the pathogenesis and tissue tropism of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Neuroinvasion and the replication of SARS-CoV-2 within the central nervous system (CNS) of K18-hACE2 mice is associated with increased mortality; although, the mechanisms by which this occurs remain unclear. In this study, we generated primary neuronal cultures from K18-hACE2 mice to investigate the effects of a SARS-CoV-2 infection. We also evaluated the immunological response to SARS-CoV-2 infection in the CNS of K18-hACE2 mice and mouse neuronal cultures. Our data show that neuronal cultures obtained from K18-hACE2 mice are permissive to SARS-CoV-2 infection and support productive virus replication. Furthermore, SARS-CoV-2 infection upregulated the expression of genes involved in innate immunity and inflammation, including IFN-α, ISG-15, CXCL10, CCL2, IL-6 and TNF-α, in the neurons and mouse brains. In addition, we found that SARS-CoV-2 infection of neurons and mouse brains activates the ZBP1/pMLKL-regulated necroptosis pathway. Together, our data provide insights into the neuropathogenesis of SARS-CoV-2 infection in K18-hACE2 mice. Full article

(This article belongs to the Section Emerging Pathogens)

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2 pages, 170 KB

Open AccessCorrection

Correction: Tanida et al. Comparative Assessment of In-House Real-Time PCRs Targeting Enteric Disease-Associated Microsporidia in Human Stool Samples. Pathogens 2021, 10, 656

by Konstantin Tanida, Andreas Hahn, Kirsten Alexandra Eberhardt, Egbert Tannich, Olfert Landt, Simone Kann, Torsten Feldt, Fred Stephen Sarfo, Veronica Di Cristanziano, Hagen Frickmann and Ulrike Loderstädt

Pathogens 2022, 11(2), 256; https://doi.org/10.3390/pathogens11020256 - 17 Feb 2022

Cited by 2 | Viewed by 1689

Abstract

In the original publication [...] Full article

(This article belongs to the Special Issue Molecular Diagnostics for Infectious Diseases)

15 pages, 3090 KB

Open AccessArticle

An Improvement in Diagnostic Blood Culture Conditions Allows for the Rapid Detection and Isolation of the Slow Growing Pathogen Yersinia pestis

by Efi Makdasi, Yafit Atiya-Nasagi, David Gur, Ayelet Zauberman, Ofir Schuster, Itai Glinert, Shlomo Shmaya, Elad Milrot, Haim Levy, Shay Weiss, Theodor Chitlaru, Emanuelle Mamroud and Orly Laskar

Pathogens 2022, 11(2), 255; https://doi.org/10.3390/pathogens11020255 - 16 Feb 2022

Cited by 5 | Viewed by 2852

Abstract

Plague, caused by the human pathogen Yersinia pestis, is a severe and rapidly progressing lethal disease that has caused millions of deaths globally throughout human history and still presents a significant public health concern, mainly in developing countries. Owing to the possibility [...] Read more.

Plague, caused by the human pathogen Yersinia pestis, is a severe and rapidly progressing lethal disease that has caused millions of deaths globally throughout human history and still presents a significant public health concern, mainly in developing countries. Owing to the possibility of its malicious use as a bio-threat agent, Y. pestis is classified as a tier-1 select agent. The prompt administration of an effective antimicrobial therapy, essential for a favorable patient prognosis, requires early pathogen detection, identification and isolation. Although the disease rapidly progresses and the pathogen replicates at high rates within the host, Y. pestis exhibits a slow growth in vitro under routinely employed clinical culturing conditions, complicating the diagnosis and isolation. In the current study, the in vitro bacterial growth in blood cultures was accelerated by the addition of nutritional supplements. We report the ability of calcium (Ca⁺²)- and iron (Fe⁺²)-enriched aerobic blood culture media to expedite the growth of various virulent Y. pestis strains. Using a supplemented blood culture, a shortening of the doubling time from ~110 min to ~45 min could be achieved, resulting in increase of 5 order of magnitude in the bacterial loads within 24 h of incubation, consequently allowing the rapid detection and isolation of the slow growing Y. pestis bacteria. In addition, the aerobic and anaerobic blood culture bottles used in clinical set-up were compared for a Y. pestis culture in the presence of Ca⁺² and Fe⁺². The comparison established the superiority of the supplemented aerobic cultures for an early detection and achieved a significant increase in the yields of the pathogen. In line with the accelerated bacterial growth rates, the specific diagnostic markers F1 and LcrV (V) antigens could be directly detected significantly earlier. Downstream identification employing MALDI-TOF and immunofluorescence assays were performed directly from the inoculated supplemented blood culture, resulting in an increased sensitivity and without any detectable compromise of the accuracy of the antibiotic susceptibility testing (E-test), critical for subsequent successful therapeutic interventions. Full article

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13 pages, 1148 KB

Open AccessArticle

Clinical Progression of Theileria haneyi in Splenectomized Horses Reveals Decreased Virulence Compared to Theileria equi

by Kelly P. Sears, Donald P. Knowles and Lindsay M. Fry

Pathogens 2022, 11(2), 254; https://doi.org/10.3390/pathogens11020254 - 16 Feb 2022

Cited by 16 | Viewed by 2601

Abstract

The global importance of the hemoparasite Theileria haneyi to equine health was recently shown by its resistance to imidocarb dipropionate (ID) and its interference with T. equi clearance by ID in some co-infected horses. Genetic characterization of T. haneyi revealed marked genomic reduction [...] Read more.

The global importance of the hemoparasite Theileria haneyi to equine health was recently shown by its resistance to imidocarb dipropionate (ID) and its interference with T. equi clearance by ID in some co-infected horses. Genetic characterization of T. haneyi revealed marked genomic reduction compared to T. equi, and initial experiments demonstrated reduced clinical severity in spleen-intact horses. Furthermore, in early experiments, splenectomized horses survived T. haneyi infection and progressed to an asymptomatic carrier state, in stark contrast to the high fatality rate of T. equi in splenectomized horses. Thus, we hypothesized that T. haneyi is less virulent than T. equi. To objectively assess virulence, clinical data from nine splenectomized, T. haneyi-infected horses were evaluated and compared to published data on T. equi-infected, splenectomized horses. Seven of eight splenectomized, T. haneyi-infected horses survived. Further, in six horses co-infected with T. equi and T. haneyi, only horses cleared of T. equi by ID survived splenectomy and became asymptomatic carriers. The reduced virulence of T. haneyi in splenectomized horses instructs why T. haneyi was, until recently, undetected. This naturally occurring comparative reduction in virulence in a natural host provides a foundation for defining virulence mechanisms of theileriosis and Apicomplexa in general. Full article

(This article belongs to the Special Issue Detection and Control Strategies for Bovine Babesiosis and Equine Piroplasmosis)

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17 pages, 2401 KB

Open AccessArticle

Patterns of Kdr-L995F Allele Emergence Alongside Detoxifying Enzymes Associated with Deltamethrin Resistance in Anopheles gambiae s.l. from North Cameroon

by Josiane Etang, Stanislas Elysée Mandeng, Philippe Nwane, Herman Parfait Awono-Ambene, Jude D. Bigoga, Wolfgang Eyisap Ekoko, Achille Jerome Binyang, Michael Piameu, Lili Ranaise Mbakop, Narcisse Mvondo, Raymond Tabue, Rémy Mimpfoundi, Jean Claude Toto, Immo Kleinschmidt, Tessa Bellamy Knox, Abraham Peter Mnzava, Martin James Donnelly and Etienne Fondjo

Pathogens 2022, 11(2), 253; https://doi.org/10.3390/pathogens11020253 - 15 Feb 2022

Cited by 5 | Viewed by 3197

Abstract

Understanding how multiple insecticide resistance mechanisms occur in malaria vectors is essential for efficient vector control. This study aimed at assessing the evolution of metabolic mechanisms and Kdr L995F/S resistance alleles in Anopheles gambiae s.l. from North Cameroon, following long-lasting insecticidal nets (LLINs) [...] Read more.

Understanding how multiple insecticide resistance mechanisms occur in malaria vectors is essential for efficient vector control. This study aimed at assessing the evolution of metabolic mechanisms and Kdr L995F/S resistance alleles in Anopheles gambiae s.l. from North Cameroon, following long-lasting insecticidal nets (LLINs) distribution in 2011. Female An. gambiae s.l. emerging from larvae collected in Ouro-Housso/Kanadi, Be-Centre, and Bala in 2011 and 2015, were tested for susceptibility to deltamethrin + piperonyl butoxide (PBO) or SSS-tributyl-phosphoro-thrithioate (DEF) synergists, using the World Health Organization’s standard protocol. The Kdr L995F/S alleles were genotyped using Hot Ligation Oligonucleotide Assay. Tested mosquitoes identified using PCR-RFLP were composed of An. arabiensis (68.5%), An. coluzzii (25.5%) and An. gambiae (6%) species. From 2011 to 2015, metabolic resistance increased in Ouro-Housso/Kanadi (up to 89.5% mortality to deltametnrin+synergists in 2015 versus <65% in 2011; p < 0.02), while it decreased in Be-Centre and Bala (>95% mortality in 2011 versus 42–94% in 2015; p < 0.001). Conversely, the Kdr L995F allelic frequencies slightly decreased in Ouro-Housso/Kanadi (from 50% to 46%, p > 0.9), while significantly increasing in Be-Centre and Bala (from 0–13% to 18–36%, p < 0.02). These data revealed two evolutionary trends of deltamethrin resistance mechanisms; non-pyrethroid vector control tools should supplement LLINs in North Cameroon. Full article

(This article belongs to the Special Issue Drug and Insecticide Resistances among Malaria Parasites and Vectors: Advances in Research and Mitigation Approaches)

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26 pages, 1787 KB

Open AccessSystematic Review

Methods Combining Genomic and Epidemiological Data in the Reconstruction of Transmission Trees: A Systematic Review

by Hélène Duault, Benoit Durand and Laetitia Canini

Pathogens 2022, 11(2), 252; https://doi.org/10.3390/pathogens11020252 - 15 Feb 2022

Cited by 14 | Viewed by 5203

Abstract

In order to better understand transmission dynamics and appropriately target control and preventive measures, studies have aimed to identify who-infected-whom in actual outbreaks. Numerous reconstruction methods exist, each with their own assumptions, types of data, and inference strategy. Thus, selecting a method can [...] Read more.

In order to better understand transmission dynamics and appropriately target control and preventive measures, studies have aimed to identify who-infected-whom in actual outbreaks. Numerous reconstruction methods exist, each with their own assumptions, types of data, and inference strategy. Thus, selecting a method can be difficult. Following PRISMA guidelines, we systematically reviewed the literature for methods combing epidemiological and genomic data in transmission tree reconstruction. We identified 22 methods from the 41 selected articles. We defined three families according to how genomic data was handled: a non-phylogenetic family, a sequential phylogenetic family, and a simultaneous phylogenetic family. We discussed methods according to the data needed as well as the underlying sequence mutation, within-host evolution, transmission, and case observation. In the non-phylogenetic family consisting of eight methods, pairwise genetic distances were estimated. In the phylogenetic families, transmission trees were inferred from phylogenetic trees either simultaneously (nine methods) or sequentially (five methods). While a majority of methods (17/22) modeled the transmission process, few (8/22) took into account imperfect case detection. Within-host evolution was generally (7/8) modeled as a coalescent process. These practical and theoretical considerations were highlighted in order to help select the appropriate method for an outbreak. Full article

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19 pages, 4275 KB

Open AccessArticle

Development of a Mouse Model to Explore CD4 T Cell Specificity, Phenotype, and Recruitment to the Lung after Influenza B Infection

by Ajitanuj Rattan, Chantelle L. White, Sean Nelson, Max Eismann, Herbey Padilla-Quirarte, Maryah A. Glover, Thamotharampillai Dileepan, Bindumadhav M. Marathe, Elena A. Govorkova, Richard J. Webby, Katherine A. Richards and Andrea J. Sant

Pathogens 2022, 11(2), 251; https://doi.org/10.3390/pathogens11020251 - 15 Feb 2022

Cited by 4 | Viewed by 3836

Abstract

The adaptive T cell response to influenza B virus is understudied, relative to influenza A virus, for which there has been considerable attention and progress for many decades. Here, we have developed and utilized the C57BL/6 mouse model of intranasal infection with influenza [...] Read more.

The adaptive T cell response to influenza B virus is understudied, relative to influenza A virus, for which there has been considerable attention and progress for many decades. Here, we have developed and utilized the C57BL/6 mouse model of intranasal infection with influenza B (B/Brisbane/60/2008) virus and, using an iterative peptide discovery strategy, have identified a series of robustly elicited individual CD4 T cell peptide specificities. The CD4 T cell repertoire encompassed at least eleven major epitopes distributed across hemagglutinin, nucleoprotein, neuraminidase, and non-structural protein 1 and are readily detected in the draining lymph node, spleen, and lung. Within the lung, the CD4 T cells are localized to both lung vasculature and tissue but are highly enriched in the lung tissue after infection. When studied by flow cytometry and MHC class II: peptide tetramers, CD4 T cells express prototypical markers of tissue residency including CD69, CD103, and high surface levels of CD11a. Collectively, our studies will enable more sophisticated analyses of influenza B virus infection, where the fate and function of the influenza B-specific CD4 T cells elicited by infection and vaccination can be studied as well as the impact of anti-viral reagents and candidate vaccines on the abundance, functionality, and localization of the elicited CD4 T cells. Full article

(This article belongs to the Topic Strategies for Prevention and Control of Influenza)

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19 pages, 1789 KB

Open AccessArticle

The Epidemiology of Sudden Oak Death Disease Caused by Phytophthora ramorum in a Mixed Bay Laurel-Oak Woodland Provides Important Clues for Disease Management

by Melina Kozanitas, Margaret R. Metz, Todd W. Osmundson, Maria Socorro Serrano and Matteo Garbelotto

Pathogens 2022, 11(2), 250; https://doi.org/10.3390/pathogens11020250 - 15 Feb 2022

Cited by 11 | Viewed by 3260

Abstract

Epidemiological models are important for the understanding of disease progression in plants and for the design of control strategies. Phytophthora ramorum, the pathogen responsible for the disease known as Sudden Oak Death, causes lethal infection on several oaks but relies on California [...] Read more.

Epidemiological models are important for the understanding of disease progression in plants and for the design of control strategies. Phytophthora ramorum, the pathogen responsible for the disease known as Sudden Oak Death, causes lethal infection on several oaks but relies on California bay laurels for transmission. Here, repeated surveys of bay laurels and oaks indicated that bay laurel disease incidence was positively correlated with rainfall, bay laurel density, and an eastern aspect, and negatively correlated with bay laurel basal area. Oak infection only occurred in years when rainfall was higher than the 30-year average, and although infection rates were greater among larger trees, mortality was greater among smaller trees. Additionally, larger oaks closer to infected bay laurels exhibited greater infection rates. Disease incidence differed among sites, and only a fraction of bay laurels were disease superspreaders, while even fewer individuals were refugial trees harboring active infections during dry periods. Based on this study, reducing bay laurel density in denser stands and the number of superspreaders or refugial trees in less dense stands may reduce disease incidence. However, the selective removal of bay laurel trees 0–10 m from oaks is likely to be more effective in preventing infection of specific oaks. Full article

(This article belongs to the Special Issue Prevention and Management of Tree Diseases)

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18 pages, 1816 KB

Open AccessReview

Hemostatic Dysfunction in Dogs Naturally Infected with Angiostrongylus vasorum—A Narrative Review

by Jakob L. Willesen, Rebecca Langhorn and Lise N. Nielsen

Pathogens 2022, 11(2), 249; https://doi.org/10.3390/pathogens11020249 - 14 Feb 2022

Cited by 15 | Viewed by 7759

Abstract

This narrative review aims to describe Angiostrongylus vasorum-induced hemostatic dysfunction of dogs with emphasis on clinical and laboratory findings as well as potential therapeutic strategies for the bleeding patient. Canine angiostrongylosis (CA) is a disease with potentially high morbidity and mortality in [...] Read more.

This narrative review aims to describe Angiostrongylus vasorum-induced hemostatic dysfunction of dogs with emphasis on clinical and laboratory findings as well as potential therapeutic strategies for the bleeding patient. Canine angiostrongylosis (CA) is a disease with potentially high morbidity and mortality in endemic areas and with fatal outcome often associated with either severe respiratory compromise, pulmonary hypertension and right-sided heart failure, or hemostatic dysfunction with severe bleeding. The most common signs of hemorrhage are hematomas, petecchiation, ecchymoses, oral mucosal membrane bleeding and scleral bleeding, while intracranial and pulmonary hemorrhage are among the most severe. The pathophysiological mechanisms underlying hemostatic dysfunction in these patients are presently researched. While the larval effect on platelets remains unknown, the parasite appears to induce dysregulation of hemostatic proteins, with studies suggesting a mixture of pro-coagulant protein consumption and hyperfibrinolysis. Importantly, not all dogs display the same hemostatic abnormalities. Consequently, characterizing the hemostatic state of the individual patient is necessary, but has proven difficult with traditional coagulation tests. Global viscoelastic testing shows promise, but has limited availability in general practice. Treatment of A. vasorum-infected dogs with hemostatic dysfunction relies on anthelmintic treatment as well as therapy directed at the individual dog’s specific hemostatic alterations. Full article

(This article belongs to the Special Issue Pathogenesis and Diagnostics of Angiostrongylus vasorum Infection)

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