Pathogens doi: 10.3390/pathogens13040286
Authors: Manami Kimijima Naoki Narisawa Eiji Hori Kengo Mandokoro Tatsuro Ito Yukina Ota Momoko Sashida Yasushi Kawai Fumio Takenaga
Streptococcus mutans is a major cariogenic organism because of its ability to form biofilms on tooth surfaces. Bacteriocins produced by S. mutans (known as mutacins) are indirect pathogenic factors that play a role in the persistence of this microbe in the oral environment. Nattokinase, a subtilisin-like alkaline serine protease, potently inhibits biofilm formation without affecting S. mutans growth. However, effective strategies utilizing nattokinase to control mutacin production by S. mutans are lacking. In this study, we evaluated the effect of nattokinase on mutacin activity in 46 strains of S. mutans with different mutacin genotypes isolated from the dental plaques of pediatric patients with caries. Nattokinase reduced the activity of mutacin against oral streptococci at a concentration of 1 mg/mL in all clinical isolates. Furthermore, nattokinase reduced the expression of non-lantibiotic mutacin structural genes (nlmABCD) and inactivated the extracellular competence-stimulating peptide involved in comDE activation, which regulates non-lantibiotic mutacin gene expression. These results suggest that nattokinase may reduce the virulence of S. mutans and could potentially be used as a new caries-preventive agent as an alternative to conventional drug treatments.
]]>Pathogens doi: 10.3390/pathogens13040285
Authors: Manuel Arce Guillermo Venegas Karla Paez Simone Latz Paola Navarrete Mario Caruffo Carmen Feijoo Katherine García Roberto Bastías
Vibrio anguillarum is a pathogen for several fish and shellfish species. Its ecology is influenced by diverse factors, including bacteriophages. Here, we identify and characterize a new temperate bacteriophage (Valp1) of V. anguillarum. Valp1 is a myovirus with a 60 nm head and a 90 nm contractile tail. Its double-stranded DNA genome of 42,988 bp contains 68 genes, including a protelomerase gene, typical of telomeric phages. Valp1 inhibits the growth of the virulent strain of V. anguillarum PF4, while the derived lysogenic strain P1.1 presents a slight reduction in its growth but is not affected by the presence of Valp1. Both strains present similar virulence in a larval zebrafish (Danio rerio) model, and only slight differences have been observed in their biochemical profile. Co-culture assays reveal that PF4 and P1.1 can coexist for 10 hours in the presence of naturally induced Valp1, with the proportion of PF4 ranging between 28% and 1.6%. By the end of the assay, the phage reached a concentration of ~108 PFU/mL, and all the non-lysogenic PF4 strains were resistant to Valp1. This equilibrium was maintained even after five successive subcultures, suggesting the existence of a coexistence mechanism between the lysogenic and non-lysogenic populations of V. anguillarum in conjunction with the phage Valp1.
]]>Pathogens doi: 10.3390/pathogens13040284
Authors: Elizabeth-Barbara Tatsi Filippos Filippatos Thomas Bello Vasiliki Syriopoulou Athanasios Michos
Sequencing of the T-cell repertoire is an innovative method to assess the cellular responses after immunization. The purpose of this study was to compare T-cell repertoires after COVID-19 immunization with homologous (HOB) and heterologous (HEB) boosting. The study included 20 participants with a median age of 27.5 (IQR:23) years, who were vaccinated with one dose of the Ad26.COV2.S vaccine and were boosted with either Ad26.COV2.S (n = 10) or BNT162b2 (n = 10) vaccine. Analysis of the T-cell receptor beta locus (TCRβ) sequencing one month after the booster dose identified that the HEB compared to the HOB group exhibited a higher number of both total and COVID-19-related functional T-cell rearrangements [mean of total productive rearrangements (TPRs): 63151.8 (SD ± 18441.5) vs. 34915.4 (SD ± 11121.6), p = 0.001 and COVID-19–TPRs: 522.5 (SD ± 178.0) vs. 298.3 (SD ± 101.1), p = 0.003]. A comparison between the HOB and HEB groups detected no statistically significant differences regarding T-cell Simpson clonality [0.021 (IQR:0.014) vs. 0.019 (IQR:0.007)], richness [8734.5 (IQR:973.3) vs. 8724 (IQR:383.7)] and T-cell fraction [0.19 (IQR:0.08) vs. 0.18 (IQR:0.08)]. HEB also exhibited a substantially elevated humoral immune response one month after the booster dose compared to HOB [median antibody titer (IQR): 10115.0 U/mL (6993.0) vs. 1781.0 U/mL (1314.0), p = 0.001]. T-cell repertoire sequencing indicated that HEB had increased SARS-CoV-2-related T-cell rearrangements, which was in accordance with higher humoral responses and possibly conferring longer protection. Data from the present study indicate that the administration of different COVID-19 vaccines as a booster may provide better protection.
]]>Pathogens doi: 10.3390/pathogens13040283
Authors: Lea Grbavac Ana Šikić Petar Kostešić Ivan-Conrado Šoštarić-Zuckermann Vesna Mojčec Perko Jadranko Boras Ingeborg Bata Andrija Musulin Tara Kostanjšak Tatjana Živičnjak
Taenia crassiceps is a zoonotic tapeworm of the genus Taenia that is distributed throughout the Northern Hemisphere. Wild and domestic carnivores are final hosts, while rodents and rabbits are primarily intermediate hosts, although many other mammals may harbour the larval stage, Cysticercus longicollis. This case report aims to describe C. longicollis infection in a lemur and molecularly characterise the isolated parasite. The excised lesion was subjected to morphological and histopathological examination, which revealed cysticerci of the tapeworm. Formalin-fixed and paraffin-embedded block (FFPEB), as well as the cysticerci fixed with formalin stored for one year, were subjected to molecular analysis, which aimed at detecting the partial mitochondrial cytochrome c oxidase subunit 1 (cox1) gene of Taenia sp. Based on the morphological characteristics, the parasite was identified as a metacestode of T. crassiceps. The presence of the cox1 gene was detected using polymerase chain reaction (PCR) in all samples. A randomly selected PCR product was sequenced and compared with other sequences from the GenBank database, confirming that the detected parasite was T. crassiceps. This article reports the first case of T. crassiceps cysticercosis in a lemur (Lemur catta) in Croatia and emphasises the potential risk of transmission from wild carnivores.
]]>Pathogens doi: 10.3390/pathogens13040282
Authors: Maria Teresa Bispo Manuela Calado Isabel Larguinho Maurício Pedro Manuel Ferreira Silvana Belo
Cercarial dermatitis (CD), or “Swimmer’s itch” as it is also known, is a waterborne illness caused by a blood fluke from the family Schistosomatidae. It occurs when cercariae of trematode species that do not have humans as their definitive host accidentally penetrate human skin (in an aquatic environment) and trigger allergic symptoms at the site of contact. It is an emerging zoonosis that occurs through water and is often overlooked during differential diagnosis. Some of the factors contributing to the emergence of diseases like CD are related to global warming, which brings about climate change, water eutrophication, the colonization of ponds by snails susceptible to the parasite, and sunlight exposure in the summer, associated with migratory bird routes. Therefore, with the increase in tourism, especially at fluvial beaches, it is relevant to analyze the current epidemiological scenario of CD in European countries and the potential regions at risk.
]]>Pathogens doi: 10.3390/pathogens13040281
Authors: José María Castillo-Castillo Pablo José Rufino-Moya Álvaro Martínez-Moreno Ángela Salvador Castaño Francisco Javier Martínez-Moreno Rafael Zafra Leva
This research work focused on the prevalence of Toxoplasma gondii in wild boar from the Sierra Morena region. We conducted an ELISA analysis using meat juice samples. A total of 892 samples from six hunting seasons (2013–2019) were collected from the provinces that constitute the Sierra Morena Mountain range. These samples were analyzed using the Pigtype® ELISA kit, specifically developed for detecting T. gondii in meat juice. The overall prevalence of T. gondii in Sierra Morena was 23.2%. The highest prevalences were observed in Córdoba (31.6%) and Jaén (25.9%). These provinces exhibit the highest density of wild boar as well as the greatest presence of the Iberian lynx (Lynx pardinus). Further in-depth studies are necessary, but it appears that the presence of wild felids and scavenger behavior may be associated with this observation.
]]>Pathogens doi: 10.3390/pathogens13040280
Authors: Wendy J. Wolters J. C. M. Vernooij Thomas M. Spliethof Jeanine Wiegel Armin R. W. Elbers Marcel A. H. Spierenburg J. Arjan Stegeman Francisca C. Velkers
This study describes clinical manifestations of highly pathogenic avian influenza (HPAI) H5N1, H5N8 and H5N6 outbreaks between 2014 and 2018 and 2020 and 2022 in the Netherlands for different poultry types and age groups. Adult duck (breeder) farms and juvenile chicken (broiler and laying pullet) farms were not diagnosed before 2020. Outbreaks in ducks decreased in 2020–2022 vs. 2014–2018, but increased for meat-type poultry. Neurological, locomotor and reproductive tract signs were often observed in ducks, whereas laying- and meat-type poultry more often showed mucosal membrane and skin signs, including cyanosis and hemorrhagic conjunctiva. Juveniles (chickens and ducks) showed neurological and locomotor signs more often than adults. Diarrhea occurred more often in adult chickens and juvenile ducks. Mortality increased exponentially within four days before notification in chickens and ducks, with a more fluctuating trend in ducks and meat-type poultry than in layers. For ducks, a mortality ratio (MR) > 3, compared to the average mortality of the previous week, was reached less often than in chickens. A lower percentage of laying flocks with MR > 3 was found for 2020–2022 vs. 2014–2018, but without significant differences in clinical signs. This study provides a basis for improvements in mortality- and clinical-sign-based early warning criteria, especially for juvenile chickens and ducks.
]]>Pathogens doi: 10.3390/pathogens13040279
Authors: Sukma Oktavianthi Aksar Chair Lages Rinaldy Kusuma Tri Shinta Kurniasih Hidayat Trimarsanto Febi Andriani David Rustandi Tandry Meriyanti Irawan Yusuf Safarina G. Malik Juandy Jo Ivet Suriapranata
The SARS-CoV-2 infection that caused the COVID-19 pandemic has become a significant public health concern. New variants with distinct mutations have emerged, potentially impacting its infectivity, immune evasion capacity, and vaccine response. A whole-genome sequencing study of 292 SARS-CoV-2 isolates collected from selected regions of Indonesia between January and October 2021 was performed to identify the distribution of SARS-CoV-2 variants and common mutations in Indonesia. During January–April 2021, Indonesian lineages B.1.466.2 and B.1.470 dominated, but from May 2021, Delta’s AY.23 lineage outcompeted them. An analysis of 7515 published sequences from January 2021 to June 2022 revealed a decline in Delta in November 2021, followed by the emergence of Omicron variants in December 2021. We identified C241T (5′UTR), P314L (NSP12b), F106F (NSP3), and D614G (Spike) mutations in all sequences. The other common substitutions included P681R (76.4%) and T478K (60%) in Spike, D377Y in Nucleocapsid (61%), and I82T in Membrane (60%) proteins. Breakthrough infection and prolonged viral shedding cases were associated with Delta variants carrying the Spike T19R, G142D, L452R, T478K, D614G, P681R, D950N, and V1264L mutations. The dynamic of SARS-CoV-2 variants in Indonesia highlights the importance of continuous genomic surveillance in monitoring and identifying potential strains leading to disease outbreaks.
]]>Pathogens doi: 10.3390/pathogens13040278
Authors: Andrea Pascual-Oliver Diego Casas-Deza Carmen Yagüe-Caballero Jose M. Arbones-Mainar Vanesa Bernal-Monterde
The eradication of the hepatitis C virus (HCV) has revolutionized the hepatology paradigm, halting the progression of advanced liver disease in patients with chronic infection and reducing the risk of hepatocarcinoma. In addition, treatment with direct-acting antivirals can reverse the lipid and carbohydrate abnormalities described in HCV patients. Although HCV eradication may reduce the overall risk of vascular events, it is uncertain whether altered lipid profiles increase the risk of cerebrovascular disease in certain patients. We have conducted a review on HCV and lipid and carbohydrate metabolism, as well as new scientific advances, following the advent of direct-acting antivirals.
]]>Pathogens doi: 10.3390/pathogens13040276
Authors: Aotong Liu Shari Garrett Wanqing Hong Jilei Zhang
Staphylococcus aureus (S. aureus) is a common pathogen that can cause many human diseases, such as skin infection, food poisoning, endocarditis, and sepsis. These diseases can be minor infections or life-threatening, requiring complex medical management resulting in substantial healthcare costs. Meanwhile, as the critically ignored “organ,” the intestinal microbiome greatly impacts physiological health, not only in gastrointestinal diseases but also in disorders beyond the gut. However, the correlation between S. aureus infection and intestinal microbial homeostasis is largely unknown. Here, we summarized the recent progress in understanding S. aureus infections and their interactions with the microbiome in the intestine. These summarizations will help us understand the mechanisms behind these infections and crosstalk and the challenges we are facing now, which could contribute to preventing S. aureus infections, effective treatment investigation, and vaccine development.
]]>Pathogens doi: 10.3390/pathogens13040277
Authors: Maria Kruglova Nikolai Nikitin Ekaterina Evtushenko Irina Matveeva Aleksandr Mazurov Igor Pavlenko Vera Popova Olesya Bogomolova Stepan Vasilyev Evgeniya Markova Yuri Fedorov
Chlamydia abortus is the etiological agent of abortion and fetal loss in sheep, goats and bovine cattle in many countries. Even though commercially available vaccines can reduce the incidence in sheep, the development of new, safe, and effective vaccines remains high on the agenda. In this study, an evaluation was made of the efficacy of a vaccine candidate, an inactivated antigen based on the extract of outer membrane proteins of a C. abortus strain known as Chlamydia VNITIBP-21, in combination with recombinant flagellin as an adjuvant. Pregnant sheep (n = 43) were divided into three groups: an experimental vaccinated group, a control infected group and a control non-infected group. The sheep were vaccinated twice, with an interval of 3 weeks, then infected with the homologous virulent strain of Chlamydia abortus on pregnancy day 75. The vaccine candidate reduced C. abortus shedding in vaginal swabs considerably, in comparison with the control group. In addition, ewes in the experimental group experienced no abortions, while those in the control group experienced instances of abortion, as well as births of weak and nonviable lambs. The findings show that the vaccine candidate proved itself to be promising in combatting the agent of ovine abortion and fetal loss.
]]>Pathogens doi: 10.3390/pathogens13040275
Authors: Z. B. Randolph Quek Sock Hoon Ng
High-throughput sequencing (HTS) has revolutionised the field of pathogen genomics, enabling the direct recovery of pathogen genomes from clinical and environmental samples. However, pathogen nucleic acids are often overwhelmed by those of the host, requiring deep metagenomic sequencing to recover sufficient sequences for downstream analyses (e.g., identification and genome characterisation). To circumvent this, hybrid-capture target enrichment (HC) is able to enrich pathogen nucleic acids across multiple scales of divergences and taxa, depending on the panel used. In this review, we outline the applications of HC in human pathogens—bacteria, fungi, parasites and viruses—including identification, genomic epidemiology, antimicrobial resistance genotyping, and evolution. Importantly, we explored the applicability of HC to clinical metagenomics, which ultimately requires more work before it is a reliable and accurate tool for clinical diagnosis. Relatedly, the utility of HC was exemplified by COVID-19, which was used as a case study to illustrate the maturity of HC for recovering pathogen sequences. As we unravel the origins of COVID-19, zoonoses remain more relevant than ever. Therefore, the role of HC in biosurveillance studies is also highlighted in this review, which is critical in preparing us for the next pandemic. We also found that while HC is a popular tool to study viruses, it remains underutilised in parasites and fungi and, to a lesser extent, bacteria. Finally, weevaluated the future of HC with respect to bait design in the eukaryotic groups and the prospect of combining HC with long-read HTS.
]]>Pathogens doi: 10.3390/pathogens13040274
Authors: Jan Bernd Hinrichs Antonia Kreitlow Lisa Siekmann Madeleine Plötz Nicole Kemper Amir Abdulmawjood
In this study, changes in hepatitis E virus (HEV) contamination in the production of liver sausage from naturally contaminated pork liver were investigated. Furthermore, the potential effectiveness of individual production parameters in reducing viral loads was measured. When processing moderately contaminated liver (initial Cq-value 29), HEV RNA persisted in the finished sausages, even after heating for 90 min at 75 °C. A matrix-specific standard curve was created using a spiking experiment to accurately quantify HEV RNA in a particularly challenging matrix like liver sausage. Variations in product-specific production parameters, including mincing and heating times, showed some reduction in contamination levels, but even prolonged heating did not render all finished products HEV negative. The persistence of HEV contamination underscores the importance of ongoing monitoring in the pig population and raw materials to enhance food safety measures and reduce the likelihood of transmission through pork consumption. The detection of HEV RNA within all processing stages of pork liver in the production of liver sausage suggests that further research into the risk of infection posed by this detection and vigilance in managing HEV risks in the food chain, particularly in pork products, are required to protect public health.
]]>Pathogens doi: 10.3390/pathogens13040273
Authors: Feyrouz Damji Kurji Ananda Sankar Bandyopadhyay Simona Zipursky Laura V. Cooper Chris Gast Margaret Toher Ralf Clemens Sue Ann Costa Clemens Rayasam Prasad Adriansjah Azhari
A sharp rise in circulating vaccine-derived poliovirus type 2 (cVDPV2) outbreaks in the years following the cessation of routine use of poliovirus type 2-containing oral polio vaccine and the trend of seeding new emergences with suboptimal vaccination response during the same time-period led to the accelerated development of the novel oral polio vaccine type 2 (nOPV2), a vaccine with enhanced genetic stability and lower likelihood of reversion to neuroparalytic variants compared to its Sabin counterpart. In November 2020, nOPV2 became the first vaccine to be granted an Emergency Use Listing (EUL) by the World Health Organization (WHO) Prequalification Team (PQT), allowing close to a billion doses to be used by countries within three years after its first rollout and leading to full licensure and WHO prequalification (PQ) in December 2023. The nOPV2 development process exemplifies how scientific advances and innovative tools can be applied to combat global health emergencies in an urgent and adaptive way, building on a collaborative effort among scientific, regulatory and implementation partners and policymakers across the globe.
]]>Pathogens doi: 10.3390/pathogens13040272
Authors: Yuanyuan Hu Caiqin Hu Shuo Wang Li Ren Yanling Hao Zheng Wang Ying Liu Junwei Su Biao Zhu Dan Li Yiming Shao Hao Liang
Since November 2021, Omicron has emerged as the dominant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, and its sublineages continue to appear one after another, significantly reducing the effectiveness of existing therapeutic neutralizing antibodies (NAbs). It is urgent to develop effective NAbs against circulating Omicron variants. Here, we isolated receptor binding domain (RBD)-specific single memory B cells via flow cytometry from a COVID-19 convalescent. The antibody variable region genes of the heavy chain (VHs) and light chain (VLs) were amplified and cloned into expression vectors. After antibody expression, ELISA screening and neutralizing activity detection, we obtained an IGHV3-53-encoded RBD-targeting cross-neutralizing antibody D6, whose VL originated from the IGKV1-9*01 germlines. D6 could potently neutralize circulating Omicron variants (BA.1, BA.2, BA.4/5 and BF.7), with IC50 values of less than 0.04 μg/mL, and the neutralizing ability against XBB was reduced but still effective. The KD values of D6 binding with RBD of the prototype and BA.1 were both less than 1.0 × 10−12 M. The protein structure of the D6-RBD model indicates that D6 interacts with the RBD external subdomain and belongs to the RBD-1 community. The sufficient contact and deep interaction of D6 HCDR3 and LCDR3 with RBD may be the crucial reason for its cross-neutralizing activity. The sorting and analysis of mAb D6 will provide important information for the development of anti-COVID-19 reagents.
]]>Pathogens doi: 10.3390/pathogens13030271
Authors: Danuta Izabela Kosik-Bogacka Krzysztof Korzeniewski Natalia Łanocha-Arendarczyk Joanna Korycińska Małgorzata Lepczyńska Ewa Dzika Małgorzata Marchelek-Myśliwiec
Intestinal parasitic infections are one of the most common infectious diseases worldwide, particularly in developing countries. A distinct group at increased risk of infection is military personnel deployed overseas for extended periods, typically six months at a time. The aim of this study was to determine the prevalence of Blastocystis spp. and other intestinal parasites in Polish military personnel returning from deployments to Lebanon (n = 206) and Iraq (n = 220). In this group of subjects, we found Blastocystis spp. (13.6%), Dientamoeba fragilis (3.3%), Entamoeba coli (0.9%), and Endolimax nana (0.5%). Entamoeba histolytica sensu lato and Chilomastix mesnili infections were detected only in one soldier returning from Lebanon and Iraq, respectively. Blastocystis subtype (ST) 3 was predominant in soldiers returning from Lebanon, followed by ST2 and ST1. ST1 infection was predominant in soldiers returning from Iraq, followed by ST3 and ST2. Our study affirms that, deployment abroad is of no influence of the prevalence of parasitic protozoa. However, it would be worth to monitor parasite infection in military personnel returning from tropical zone even if they have no actual symptoms. In addition, it is very important to determine the subtypes of Blastocystis—this may help to clearly define their pathogenicity, especially considering the scarcity of studies on Blastocystis genotypes in Iraqi and Lebanese residents.
]]>Pathogens doi: 10.3390/pathogens13030270
Authors: Jana C. Klink Alexandra Rieger Peter Wohlsein Ursula Siebert Anna Obiegala
Raccoon dogs (Nyctereutes procyonoides) and raccoons (Procyon lotor) are invasive alien species originating from East Asia and North America, respectively. They are discussed as vectors and reservoirs for various infectious diseases, including vector-borne and zoonotic pathogens, and are therefore a potential threat to human and domestic animal health, as well as to biodiversity and conservation. In the years 2021 and 2022, 110 raccoon dogs (Nyctereutes procyonoides) and 30 raccoons (Procyon lotor) were screened via qPCR for the presence of Leptospira spp., Rickettsia spp. and Borreliella spp. in the German federal state of Schleswig-Holstein as part of a health and risk assessment study. Borreliella spp. were confirmed in one raccoon dog and one raccoon, identified as Borreliella afzelii in the raccoon. Leptospira spp. were found in 21 (19.44%) raccoon dogs and 2 (6.90%) raccoons. In five raccoon dogs, Leptospira spp. were identified as Leptospira borgpetersenii, Leptospira kirschneri and Leptospira interrogans.
]]>Pathogens doi: 10.3390/pathogens13030269
Authors: Petros Ioannou Stella Baliou Diamantis P. Kofteridis
Wickerhamomyces anomalus has been previously classified as Hansenula anomala, Pichia anomala, and Candida pelliculosa and was recently reclassified in the genus Wickerhamomyces after phylogenetic analysis of its genetic sequence. An increasing number of reports of human infections by W. anomalus have emerged, suggesting that this microorganism is an emerging pathogen. The present review aimed to provide data on the epidemiology, antifungal resistance, clinical characteristics, treatment, and outcomes of fungemia by W. anomalus by extracting all the available information from published original reports in the literature. PubMed/Medline, Cochrane Library, and Scopus databases were searched for eligible articles reporting data on patients with this disease. In total, 36 studies involving 170 patients were included. The age of patients with fungemia by W. anomalus ranged from 0 to 89 years; the mean age was 22.8 years, the median age was 2.2 years, with more than 37 patients being less than one month old, and 54% (88 out of 163 patients) were male. Regarding patients’ history, 70.4% had a central venous catheter use (CVC), 28.7% were on total parenteral nutrition (TPN), 97% of neonates were hospitalized in the neonatal ICU (NICU), and 39.4% of the rest of the patients were hospitalized in the intensive care unit (ICU). Previous antimicrobial use was noted in 65.9% of patients. The most common identification method was the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) in 34.1%, VITEK and VITEK 2 in 20.6%, and ID32 C in 15.3%. W. anomalus had minimal antifungal resistance to fluconazole, echinocandins, and amphotericin B, the most commonly used antifungals for treatment. Fever and sepsis were the most common clinical presentation noted in 95.8% and 86%, respectively. Overall mortality was 20% and was slightly higher in patients older than one year. Due to the rarity of this disease, future multicenter studies should be performed to adequately characterize patients’ characteristics, treatment, and outcomes, which will increase our understanding and allow drawing safer conclusions regarding optimal management.
]]>Pathogens doi: 10.3390/pathogens13030268
Authors: Benjamin Jacob Edwin Michael Thomas R. Unnasch
Onchocerciasis, or river blindness, has historically been one of the most important causes of blindness worldwide, and a major cause of socio-economic disruption, particularly in sub-Saharan Africa. Its importance as a cause of morbidity and an impediment to economic development in some of the poorest countries in the world motivated the international community to implement several programs to control or eliminate this scourge. Initially, these involved reducing transmission of the causative agent Onchocerca volvulus through controlling the vector population. When ivermectin was found to be a very effective drug for treating onchocerciasis, the strategy shifted to mass drug administration (MDA) of endemic communities. In some countries, both vector control and ivermectin MDA have been used together. However, traditional vector control methods involve treating rivers in which the black fly vectors breed with insecticides, a process which is expensive, requires trained personnel to administer, and can be ecologically harmful. In this review, we discuss recent research into alternatives to riverine insecticide treatment, which are inexpensive, ecologically less harmful, and can be implemented by the affected communities themselves. These can dramatically reduce vector densities and, when combined with ivermectin MDA, can accelerate the time to elimination when compared to MDA alone.
]]>Pathogens doi: 10.3390/pathogens13030267
Authors: Mateusz Babicki Damian Kołat Żaneta Kałuzińska-Kołat Joanna Kapusta Agnieszka Mastalerz-Migas Piotr Jankowski Michał Chudzik
SARS-CoV-2 has acquired many mutations that influence the severity of COVID-19’s course or the risk of developing long COVID. In 2022, the dominant SARS-CoV-2 variant was Omicron. This study aimed to compare the course of COVID-19 in the periods before and during the dominance of the Omicron variant. Risk factors for developing long COVID were also assessed. This study was based on stationary visits of patients after COVID-19 and follow-up assessments after 3 months. Clinical symptoms, comorbidities, and vaccination status were evaluated in 1967 patients. Of the analyzed group, 1308 patients (66.5%) were affected by COVID-19 in the period before the Omicron dominance. The prevalence of long COVID was significantly lower among patients of the Omicron group (47.7% vs. 66.9%, p < 0.001). The risk of long COVID was higher for women (OR: 1.61; 95% CI: 1.31, 1.99]) and asthmatics (OR: 1.46; 95% CI: 1.03, 2.07]). Conclusively, infection during the Omicron-dominant period was linked to a lower risk of developing long COVID. Females are at higher risk of developing long COVID independent of the pandemic period. Individuals affected by COVID-19 in the Omicron-dominant period experience a shorter duration of symptoms and reduced frequency of symptoms, except for coughing, which occurs more often.
]]>Pathogens doi: 10.3390/pathogens13030266
Authors: Po-Yuan Ke
Autophagy plays a fundamental role in maintaining cellular homeostasis by eliminating intracellular components via lysosomes. Successful degradation through autophagy relies on the fusion of autophagosomes to lysosomes, which leads to the formation of autolysosomes containing acidic proteases that degrade the sequestered materials. Viral infections can exploit autophagy in infected cells to balance virus–host cell interactions by degrading the invading virus or promoting viral growth. In recent years, cumulative studies have indicated that viral infections may interfere with the fusion of autophagosomes and lysosomes, thus benefiting viral replication and associated pathogenesis. In this review, I provide an overview of the current understanding of the molecular mechanism by which human viral infections deregulate autophagosome–lysosome fusion and summarize the physiological significance in the virus life cycle and host cell damage.
]]>Pathogens doi: 10.3390/pathogens13030265
Authors: Aris P. Agouridis Christina Mastori-Kourmpani Polyna Antoniou Paschalis Konstantinou Evangelos C. Rizos Constantinos Tsioutis
Background: Beau’s lines are transverse grooves in the nail plate that result from transient interruption of the growth of the proximal nail matrix after severe disease. The aim of this study is to systematically report all evidence on the association of Beau’s lines with COVID-19 infection or vaccination against COVID-19. Methods: PubMed and Scopus databases were searched up to January 2024 for articles reporting Beau’s lines associated with COVID-19 infection or vaccination for COVID-19. PROSPERO ID: CRD42024496830. Results: PubMed search identified 299 records while Scopus search identified 18 records. After screening the bibliography, nine studies including 35 cases were included in our systematic review. The studies were reported from different areas around the world. Included studies documented Beau’s lines following COVID-19 vaccination (two studies) or after COVID-19 infection (seven studies). High variability was recorded in onset and resolution times among included cases, averaging 3 months and 6 months after COVID-19 infection, respectively. In the two studies reporting Beau’s lines after vaccination, onset was at 7 days and 6 weeks and resolution occurred after 8 and 17 weeks, respectively. Conclusions: To the best of our knowledge, this is the first systematic review reporting the association of Beau’s lines with COVID-19 infection and vaccination. Severe immune response can result in the formation of these nail disorders. Of importance, Beau’s lines represent a potential indicator of prior severe COVID-19 infection or vaccination for COVID-19, as well as a sign of long COVID-19 syndrome.
]]>Pathogens doi: 10.3390/pathogens13030264
Authors: Uwem Etop George Temitope O. C. Faleye Lander De Coninck Sheriff Tunde Agbaje Ijeoma Maryjoy Ifeorah Bernard Anyebe Onoja Elijah Igbekele Oni Adebowale Oluseyi Olayinka Toluwani Goodnews Ajileye Arthur Obinna Oragwa Toluwanimi Emmanuel Akinleye Bolutife Olubukola Popoola Oluwadamilola Gideon Osasona Olaitan Titilola Olayinka Oluwadamilola Adefunke George Ahmed Iluoreh Muhammad Isaac Komolafe Adekunle Johnson Adeniji Jelle Matthijnssens Moses Olubusuyi Adewumi
Using a metagenomic sequencing approach on stool samples from children with Acute Flaccid Paralysis (AFP), we describe the genetic diversity of Sapoviruses (SaVs) in children in Nigeria. We identified six complete genome sequences and two partial genome sequences. Several SaV genogroups and genotypes were detected, including GII (GII.4 and GII.8), GIV (GIV.1), and GI (GI.2 and GI.7). To our knowledge, this is the first description of SaV infections and complete genomes from Nigeria. Pairwise identity and phylogenetic analysis showed that the Nigerian SaVs were related to previously documented gastroenteritis outbreaks with associated strains from China and Japan. Minor variations in the functional motifs of the nonstructural proteins NS3 and NS5 were seen in the Nigerian strains. To adequately understand the effect of such amino acid changes, a better understanding of the biological function of these proteins is vital. The identification of distinct SaVs reinforces the need for robust surveillance in acute gastroenteritis (AGE) and non-AGE cohorts to better understand SaVs genotype diversity, evolution, and its role in disease burden in Nigeria. Future studies in different populations are, therefore, recommended.
]]>Pathogens doi: 10.3390/pathogens13030263
Authors: Wei-Chuan Chen Yusen Eason Lin
The COVID-19 pandemic has underscored the pivotal role of epidemiology in studying pathogenic agents [...]
]]>Pathogens doi: 10.3390/pathogens13030262
Authors: Jean-Yves Ekra Eliakunda Michael Mafie Edouard K. N’Goran Dramane Kaba Biégo Guillaume Gragnon Jagan Srinivasan
The potential danger to livestock from African animal trypanosomiasis is well known. However, the trypanosome species circulating in cattle and their genetics are poorly understood. After different alignments according to three regions (ITS1, gGAPDH and rRNA gene) of the trypanosome genome, phylogenetic analyses were used to show the genetic diversity of the different species that were circulating in the cattle in three regions (Bagoue, Poro and Tchologo) of Côte d’Ivoire. These analyses were performed by alignment of ITS1; by alignment of partial 18S, ITS1, 5.8S, ITS2 and partial 28S rRNA genes; and by alignment of gGAPDH gene with sequences of Trypanosomes found in GenBank. Three species were identified (T. vivax, T. theileri and T. congolense) in the cattle in the three northern regions of Côte d’Ivoire. T. vivax and T. theileri were the most abundant species in the present study. Contrary to the other primers used in this study, the ITS1 primers were not able to amplify T. theileri. We observed mixed infections between T. theileri and the other two species identified (T. vivax and T. congolense). As far as primers are concerned, in some cases, rRNA was able to identify the same species of trypanosomes that the ITS1 and gGAPDH primers were able to identify. Two main distinct groups of T. theileri complex were identified. The T. congolense and T. vivax strains were close to African strains, such as those from Kenya, Nigeria and Cameroon, unlike the T. theileri strain. Three trypanosome species (T. vivax, T. theileri and T. congolense) circulate in cattle in the Savannah district of Côte d’Ivoire. The genetic diversity of the trypanosome species encountered in this study cannot be classified as intraspecies according to geographical area and breed of cattle they infect.
]]>Pathogens doi: 10.3390/pathogens13030261
Authors: Vanessa van Meer Janusz T. Pawęska Robert Swanepoel Antoinette Grobbelaar Armanda D. Bastos
From 1993 to 1994, 64 free-ranging elephants (Loxodonta africana) succumbed to encephalomyocarditis in the Kruger National Park, South Africa, of which 83% were adult bulls. Mastomys rodents were implicated as the reservoir host of the Encephalomyocarditis virus (EMCV) based on serology and RT-PCR. However, in the absence of sequence-confirmation of both the virus and the rodent host, definitive links between the elephant outbreak strains and rodent reservoir could not be established. In this study, we generate the first reference genome sequences for three historical EMCVs isolated from two Mastomys rodents and one Mastomys-associated mite, Laelaps muricola, in Gauteng Province, South Africa, in 1961. In addition, near-complete genome sequences were generated for two elephant outbreak virus strains, for which data were previously limited to the P1 and 3D genome regions. The consensus sequence of each virus was determined using a PCR-Sanger sequencing approach. Phylogenetic analysis confirmed the three near-identical (99.95–99.97%) Mastomys-associated viruses to be sister to the two near-identical (99.85%) elephant outbreak strains, differing from each other at 6.4% of sites across the ~7400-nucleotide region characterised. This study demonstrates a link between Mastomys-associated viruses and the historical elephant outbreak strains and implicates Mastomys as reservoirs of EMCV in South Africa.
]]>Pathogens doi: 10.3390/pathogens13030260
Authors: Gabriel da Silva Oliveira Concepta McManus Igor Rafael Ribeiro Vale Vinícius Machado dos Santos
Essential oils are liquids containing non-toxic compounds that are unfavorable to the growth of microorganisms. They are sold globally at affordable or very high prices, depending on the availability and type of plant, the scale of production, the extraction method, costs associated with logistics and electricity consumption, among other variables. Each year, the quantity of research dedicated to the antimicrobial potential of essential oils in poultry farming is expanding. Researchers consensually relay that this increase is due to the growing resistance of microorganisms to traditional antimicrobials and concerns about the toxicity of these products. This review proposes an analysis of the antimicrobial feasibility of using essential oils to address microbial challenges in poultry farms, aiming to ensure the production and supply of microbiologically safe hatching eggs. Based on the findings in the literature, in addition to following other necessary precautions in the daily routines of poultry farming practices, developing an antimicrobial control program with essential oils that integrates poultry facilities, poultry and hatching eggs, adapted to the particularities of each context seems to be extremely effective.
]]>Pathogens doi: 10.3390/pathogens13030259
Authors: Abarna Thangaraj Reva Tyagi Deepti Suri Sudhir Gupta
Primary immune regulatory disorders (PIRDs) constitute a spectrum of inborn errors of immunity (IEIs) that are primarily characterized by autoimmunity, lymphoproliferation, atopy, and malignancy. In PIRDs, infections are infrequent compared to other IEIs. While susceptibility to infection primarily stems from antibody deficiency, it is sometimes associated with additional innate immune and T or NK cell defects. The use of immunotherapy and chemotherapy further complicates the immune landscape, increasing the risk of diverse infections. Recurrent sinopulmonary infections, particularly bacterial infections such as those associated with staphylococcal and streptococcal organisms, are the most reported infectious manifestations. Predisposition to viral infections, especially Epstein–Barr virus (EBV)-inducing lymphoproliferation and malignancy, is also seen. Notably, mycobacterial and invasive fungal infections are rarely documented in these disorders. Knowledge about the spectrum of infections in these disorders would prevent diagnostic delays and prevent organ damage. This review delves into the infection profile specific to autoimmune lymphoproliferative syndrome (ALPS), Tregopathies, and syndromes with autoimmunity within the broader context of PIRD. Despite the critical importance of understanding the infectious aspects of these disorders, there remains a scarcity of comprehensive reports on this subject.
]]>Pathogens doi: 10.3390/pathogens13030258
Authors: Luciano Michaël Tantely Soa Fy Andriamandimby Maminirina Fidelis Ambinintsoa Manou Rominah Raharinirina Jean Théophile Rafisandratantsoa Jean-Pierre Ravalohery Aina Harimanana Nirina Nantenaina Ranoelison Judickaelle Irinantenaina Miamina Fidy Ankasitrahana Dany Bakoly Ranoaritiana Laurence Randrianasolo Rindra Vatosoa Randremanana Vincent Lacoste Philippe Dussart Romain Girod
A Rift Valley fever (RVF) outbreak occurred in at least five regions of Madagascar in 2021. The aim of this study was to provide an overview of the richness, abundance, ecology, and trophic preferences of mosquitoes in the Mananjary district and to investigate the distribution of mosquitoes that were RT-PCR-positive for RVFV. Three localities were prospected from 26 April to 4 May 2021, using light traps, BG-Sentinel traps baited with an artificial human odor, Muirhead-Thomson pit traps, and indoor pyrethroid spray catches. A total of 2806 mosquitoes belonging to at least 26 species were collected. Of 512 monospecific pools of mosquitoes tested with real-time RT-PCR, RVFV was detected in 37 pools representing 10 mosquito species. The RVFV-positive species were as follows: Aedes albopictus, Ae. argenteopunctatus, Anopheles coustani, An. gambiae s.l., An. mascarensis, An. squamosus/cydippis, Culex antennatus, Cx. decens, Cx. Tritaeniorhynchus, and Uranotaenia spp. Of the 450 tested engorged females, 78.7% had taken a blood meal on humans, 92.9% on cattle, and 71.6% had taken mixed (human–cattle) blood meals. This investigation suggests the potential role of mosquitoes in RVFV transmission within this epizootic/epidemic context and that the human populations at the three study sites were highly exposed to mosquitoes. Therefore, the use of impregnated mosquito nets as an appropriate prevention method is recommended.
]]>Pathogens doi: 10.3390/pathogens13030257
Authors: Aina Nirina Harimanana Soa Fy Andriamandimby Dany Bakoly Ranoaritiana Laurence Randrianasolo Judickaelle Irinantenaina Nirina Nantenaina Ranoelison Jean Théophile Rafisandrantatsoa Miamina Fidy Ankasitrahana Antso Hasina Raherinandrasana Manuela Vololoniaina Andriamahatana Michael Luciano Tantely Romain Girod Philippe Dussart Vincent Lacoste Rindra Vatosoa Randremanana
An epizootic of rift valley fever (RVF) was suspected on 21 February 2021 in various districts of Madagascar, with a lab confirmation on 1 April 2021. A cross-sectional survey aiming to detect cases of RVF in humans and to study the circulation of rift valley fever virus (RVFV) in animals was conducted from 22 April to 4 May 2021 in the district of Mananjary. Blood samples from cattle and humans were tested using serological and molecular techniques. In cattle, the circulation of RVFV was confirmed between 5 February and 4 May 2021. The positivity rates of anti-RVFV IgG and IgM were 60% and 40%, respectively. In humans, the circulation of RVFV was observed from 1 April to 5 May 2021. The positivity rate of RVFV was estimated to be 11.7% by combining the results of the molecular and serological approaches. Of the 103 individuals who agreed to participate in the survey, 3 were determined to be positive by RT-PCR, and 10 had anti-RVFV IgM. Among them, one was positive for both. Given that previous studies have reported the circulation of RVFV during inter-epidemic periods and the occurrence of outbreaks due to imported RVFV in Madagascar, our findings suggest the importance of strengthening RVF surveillance from a “One Health” perspective by conducting syndromic and risk-based surveillance at the national and regional levels.
]]>Pathogens doi: 10.3390/pathogens13030256
Authors: Karolina Zimmer Alicja M. Chmielewska Paulina Jackowiak Marek Figlerowicz Krystyna Bienkowska-Szewczyk
The glycosylation of viral envelope proteins plays an important role in virus biology and the immune response of the host to infection. Hepatitis C virus (HCV) envelope proteins E1 and E2, key players in virus entry and spread, are highly N-glycosylated and possess 4 (5 in certain genotypes) to 11 conserved glycosylation sites, respectively. Many published results based on recombinant proteins indicate that the glycan shield can mask the epitopes targeted by neutralizing antibodies. Glycan shifting within the conserved linear E2 region (412–423) could be one of the escape strategies used by HCV. In the present report, we isolated E2 genes from samples (collected before the IFN-RBV therapy) originating from pediatric patients infected with HCV gt 1a. We analyzed the biochemical properties of cloned E2 glycoprotein variants and investigated their glycosylation status. The sequencing of E2 genes isolated from patients who did not respond to therapy revealed mutations at N-glycosylation sites, thus leading to a lower molecular weight and a low affinity to both linear and conformational neutralizing antibodies. The loss of the glycosylation site within the conserved epitope (amino acid 417) impaired the binding with AP33, an antibody that potently neutralizes all genotypes of HCV. Our findings, based on clinical samples, confirm the influence of N-glycosylation aberrations on the antigenic and conformational properties of HCV E1/E2, which may possibly correlate with the outcome of therapy in patients.
]]>Pathogens doi: 10.3390/pathogens13030255
Authors: Tatiane Alves Barbosa Silvana Carvalho Thiengo Monica Ammon Fernandez Jucicleide Ramos-de-Souza Suzete Rodrigues Gomes
Metastrongyloidea includes nematodes that parasitize mammals, mainly infecting their respiratory and cardiovascular systems, and are responsible for emerging zoonosis in the world. Terrestrial mollusks are their main intermediate hosts, with few exceptions. Here we present the results of a malacological survey to know the distribution of Angiostrongylus cantonensis in Macapá, Amapá, in the Brazilian Amazon region, after the report of a case of eosinophilic meningitis in 2018. Mollusks were collected in 45 neighborhoods between March 2019 and February 2020. They were identified, parasitologically analyzed, and their nematodes parasites were identified based on the morphology and MT-CO1 sequencing. Infections of An. cantonensis were observed in Achatina fulica, Sarasinula linguaeformis and Subulina octona. These are the first records of the natural infection of the last two species by An. cantonensis in the Brazilian Amazon region. The angiostrongylid Aelurostrongylus abstrusus, which parasitizes cats, was also detected parasitizing A. fulica and Diplosolenodes occidentalis. This is also the first record of the slug D. occidentalis infected by Ae. abstrusus. The highest infection rates were recorded in neighborhoods where the environment conditions favor the proliferation of both mollusks and rodents. The results demonstrate the ample distribution of An. cantonensis in Macapá and the need for surveillance and mollusk vector control in Brazil and other countries.
]]>Pathogens doi: 10.3390/pathogens13030254
Authors: Martyna Biała Joanna Nieleńczuk Anna Chodorowska Bartosz Szetela
Toxocariasis is the parasitic infection caused by the larvae of Toxocara roundworms species: Toxocara canis from dogs and, less frequently, Toxocara cati from cats. The high proportion of asymptomatic cases of toxocariasis and the uncharacteristic clinical manifestations mimicking other medical conditions make diagnosis challenging. The main clinical presentations of toxocariasis are visceral and ocular larva migrans. Migration to the central nervous system (neurotoxocariasis) is rare and can cause meningitis, encephalitis, myelitis, cerebral vasculitis, seizures, headache or asymptomatic CNS infection. Neurotoxocariasis is an uncommon diagnosis and it is probably underdiagnosed due to the nonspecific clinical manifestations, low awareness of physicians as well as the lack of standardized diagnostic exams. To date, no causality has been proven between neurotoxocariasis and aneurysms, but due to the character of immune response elicited by the parasites, it remains an important possibility for further research. We present a case report of a woman infected with Toxocara canis highlighting the diagnostic difficulties. We aim to raise the awareness of the clinical symptomatology of neurotoxocariasis.
]]>Pathogens doi: 10.3390/pathogens13030252
Authors: Alexandr Senyagin Nadezhda Sachivkina Milana Das Anna Arsenyuk Ramziya Mannapova Alfir Mannapov Tursumbai Kubatbekov Dmitriy Svistunov Olesya Petrukhina Andrey Zharov Natallia Zhabo
Urinary tract infections occupy a special niche among diseases of infectious etiology. Many microorganisms associated with urinary tract infections, such as Klebsiella oxytoca, Enterococcus spp., Morganella morganii, Moraxella catarrhalis, Pseudomonas aeruginosa, Proteus mirabilis, Staphylococcus aureus, Staphylococcus spp., and Candida spp., can form biofilms. The aim of this research was to study the effect of the enzyme L-lysine-Alpha-oxidase (LO) produced by the fungus Trichoderma harzianum Rifai on the biofilm formation process of microorganisms associated with urinary tract infections. Homogeneous LO showed a more pronounced effect than the culture liquid concentrate (cCL). When adding samples at the beginning of incubation, the maximum inhibition was observed in relation to Enterococcus faecalis 5960—cCL 86%, LO 95%; Enterococcus avium 1669—cCL 85%, LO 94%; Enterococcus cloacae 6392—cCL 83%, LO—98%; and Pseudomonas aeruginosa 3057—cCL 70%, LO—82%. The minimum inhibition was found in Candida spp. Scanning electron microscopy was carried out, and numerous morphological and structural changes were observed in the cells after culturing the bacterial cultures in a medium supplemented with homogeneous LO. For example, abnormal division was detected, manifesting as the appearance of joints in places where the bacteria diverge. Based on the results of this work, we can draw conclusions about the possibility of inhibiting microbial biofilm formation with the use of LO; especially significant inhibition was achieved when the enzyme was added at the beginning of incubation. Thus, LO can be a promising drug candidate for the treatment or prevention of infections associated with biofilm formation.
]]>Pathogens doi: 10.3390/pathogens13030253
Authors: Emily Onizawa Cheryl Jenkins
For over a decade, bovine anaemia caused by Theileria orientalis Ikeda has been a significant disease in the Australian cattle industry. In this study, we conducted a spatial and temporal analysis of theileriosis in Australia using historic data from submissions to the New South Wales Department of Primary Industries (NSW DPI) from 2006 to 2022, where herd history, clinical signs, and PCR results were available. Since the first detections of bovine theileriosis in the Sydney area in 2006, the disease spread north- and southward and is now endemic to the southeast coast of Australia, closely mirroring the distribution of the principal vector Haemaphysalis longicornis. Across all years, the prevalence of the Ikeda genotype was 88%, while the prevalence of the benign Chitose and Buffeli genotypes was 55% and 38%, respectively. The majority of submissions were from beef cattle in coastal NSW, with anaemia, fever, jaundice, abortion, and lethargy the most frequently reported clinical signs. Transportation was identified as the major risk factor for disease. Until 2015, the majority of cases were reported in adult cattle, while in later years, calves made up the majority of cases, most likely due to the widespread acquisition of immunity in adults. Calves were significantly more likely to present with diarrhoea, lethargy, and anaemia, and to suffer mortality, while adults were significantly more likely to present with jaundice. Instances of abortion were observed to be significantly associated with beef cattle. The relationship between the level of parasitaemia and anaemia revealed a strong negative correlation for all animals examined.
]]>Pathogens doi: 10.3390/pathogens13030251
Authors: Marek Matras Magdalena Stachnik Anna Kycko Magdalena Wasiak Ewa Paździor Joanna Maj-Paluch Ewa Borzym Michał Reichert
Every year, ulcerative dermal necrosis (UDN) affects salmonids that spend most of their lives in the sea during their migration to the rivers of northern Poland to spawn. The clinical form of the disease manifests itself in ulcerative skin lesions, which lead to significant weakening of the fish and, in most cases, result in their death. This study was carried out on samples taken from sea trout in the Słupia River in northern Poland. In order to identify the pathogen, experiments on the transmission of the disease were carried out, and additional histopathological, microbiological and electron microscopic examinations were performed. As a result of these studies, it was possible to experimentally transfer the disease from sick to healthy fish. The results indicate a complex etiology of the disease (lack of a clearly defined pathogen), in which the change in the environment from salty to freshwater triggers the related changes in skin physiology, which are the main causes of increased susceptibility to the development of the disease.
]]>Pathogens doi: 10.3390/pathogens13030250
Authors: Sandra Cristino Maria Rosaria Pascale Federica Marino Carlo Derelitto Silvano Salaris Massimiliano Orsini Stefano Squarzoni Antonella Grottola Luna Girolamini
Two Legionella-like isolates, 8cVS16T and 9fVS26, were isolated from a water distribution system (WDS) in a healthcare facility. Cells were Gram- and Ziehl Neelsen-stain-negative, rod-shaped, motile, and exhibited a blue-white fluorescence under Wood’s lamp at 365 nm. The strains grew in a range of 32–37 °C on BCYE with L-cysteine (Cys+), GVPC, and MWY agar medium, with a positive reaction for oxidase, catalase, and gelatinase. The dominant fatty acids were summed features 3 (C16:1ω7c/C16:1ω6c) (27.7%), C16:0 iso (17.5%), and C16:0 (16.3%), and Q13 as the major ubiquinone. The mip and rpoB gene sequences showed a similarity of 96.7% and 92.4%, with L. anisa (ATCC 35292T). The whole genomes sequencing (WGS) performed displayed a GC content of 38.21 mol% for both. The digital DNA-DNA hybridization (dDDH) analysis demonstrated the separation of the two strains from the phylogenetically most related L. anisa (ATCC 35292T), with ≤43% DNA-DNA relatedness. The Average Nucleotide Identity (ANI) between the two strains and L. anisa (ATCC 35292T) was 90.74%, confirming that the two isolates represent a novel species of the genus Legionella. The name proposed for this species is Legionella resiliens sp. nov., with 8cVS16T (=DSM 114356T = CCUG 76627T) as the type strain.
]]>Pathogens doi: 10.3390/pathogens13030249
Authors: Flora De Conto
Influenza is one of the most prevalent causes of death worldwide. Influenza A viruses (IAVs) naturally infect various avian and mammalian hosts, causing seasonal epidemics and periodic pandemics with high morbidity and mortality. The recent SARS-CoV-2 pandemic showed how an animal virus strain could unpredictably acquire the ability to infect humans with high infection transmissibility. Importantly, highly pathogenic avian influenza A viruses (AIVs) may cause human infections with exceptionally high mortality. Because these latter infections pose a pandemic potential, analyzing the ecology and evolution features of host expansion helps to identify new broad-range therapeutic strategies. Although IAVs are the prototypic example of molecular strategies that capitalize on their coding potential, the outcome of infection depends strictly on the complex interactions between viral and host cell factors. Most of the studies have focused on the influenza virus, while the contribution of host factors remains largely unknown. Therefore, a comprehensive understanding of mammals’ host response to AIV infection is crucial. This review sheds light on the involvement of the cellular cytoskeleton during the highly pathogenic AIV infection of mammalian hosts, allowing a better understanding of its modulatory role, which may be relevant to therapeutic interventions for fatal disease prevention and pandemic management.
]]>Pathogens doi: 10.3390/pathogens13030248
Authors: Aleksandra Górzyńska Kamila Kondracka Agnieszka Korzeniowska-Kowal Urszula Nawrot
(1) Background: Despite being considered a non-pathogenic yeast, recently, a growing occurrence of Saccharomyces cerevisiae infections has been noted. There is little knowledge about the drug susceptibility of this species. Therefore, the objective of this research was to expand it and determine the drug susceptibility profile of a local collection of clinical isolates of this species. (2) Methods: This study contained 55 clinical isolates identified as Saccharomyces cerevisiae using the MALDI-TOF method. The susceptibility of Saccharomyces cerevisiae was tested to 10 antifungals (amphotericin B, flucytosine, fluconazole, voriconazole, posaconazole, micafungin, anidulafungin, caspofungin, and itraconazole) using MICRONAUT-AT tests and manogepix, a new drug, using the microdilution method according to EUCAST. (3) Results: Overall, most strains were classified as sensitive to amphotericin B and flucytosine (MIC ranges of ≤0.03–1 and ≤0.06–0.125, respectively) and also to echinocandins. However, five isolates expressed high MIC values for all of the tested azoles, indicating cross-resistance. The MIC range for manogepix was 0.001–0.125 mg/L, with an MIC50 of 0.03 mg/L and an MIC90 of 0.06 mg/L. (4) Conclusions: The occurrence of resistance to azoles may be a concerning problem and therefore should be investigated further. However, the new antifungal manogepix appears to be an interesting new therapeutic option for treating such infections.
]]>Pathogens doi: 10.3390/pathogens13030247
Authors: Adamu Isah Gano Siti Zubaidah Ramanoon Nor-Azlina Abdul Aziz Mazlina Mazlan Mohd Rosly Shaari Abdullahi Aliyu Muhammad Bashir Bello Mustapha Umar Imam Hazilawati Hamzah
Bovine babesiosis has substantial economic implications in the cattle industry, emphasizing the need for a thorough understanding of the genetic diversity of the causative apicomplexan pathogen. Although babesiosis has been extensively studied globally, the genetic diversity of Babesia species in Malaysian and Nigerian cattle remains unreported. This study aims to bridge this gap by detecting and characterizing Babesia species in selected cattle herds. Our investigation explores the genetic diversity of Babesia species in cattle from Selangor, Malaysia, and Ribah, Nigeria. Blood samples revealed a 32.9% infection rate via PCR analysis. Further genetic analysis detected variations in Malaysian Babesia bigemina isolates but genetic similarity among Nigerian isolates. Conversely, all Babesia bovis isolates displayed genetic homogeneity. In summary, this research identifies genetic diversity in Babesia species affecting Malaysian and Nigerian cattle, highlighting regional disparities.
]]>Pathogens doi: 10.3390/pathogens13030246
Authors: Henrique C. Teixeira Giulia P. C. Valle Rouzbeh Mahdavi Priscila S. M. Dias Erick E. de Oliveira Cristina P. Aira Daniela Heinz Andreas Latz Marta de Lana Fernanda N. Morgado Renato Porrozzi Ulrich Steinhoff
The diagnosis of canine leishmaniasis (CanL) still represents a challenge due to the variable clinical manifestations and the large number of asymptomatic dogs. Serological tests are most commonly used to detect infected animals, revealing anti-Leishmania antibodies, mainly of the IgG isotype. Recently, a new diagnostic antigen, rKLi8.3, containing 8.3 kinesin tandem repeats (TR) from a Leishmania infantum strain from Sudan, has been shown to provide excellent specificity and sensitivity for the detection of Leishmania-infected humans and dogs. However, asymptomatic animals with very low antibody titers are often difficult to detect by serodiagnosis. Thus, we wondered whether the addition of an anti-IgG-enhancing step in the protein A/G-based rKLi8.3-ELISA will improve the diagnostic performance without decreasing the specificity. For this, parasitologically confirmed CanL cases with low or high clinical scores, uninfected healthy controls and dogs with other infections were tested by rKLi8.3-ELISA as well as two different immunochromatographic rapid tests, rKLi8.3-lateral flow test (LFT) and Dual Path Platform (DPP®) based on the rK28 antigen. Our results show that the diagnostic accuracies of the rKLi8.3-ELISA and LFT were similar to that of DPP, missing several asymptomatic animals. However, the addition of a secondary, amplifying anti-dog IgG antibody in the protein A/G-based rKLi8.3-ELISA enabled the detection of nearly all asymptomatic dogs without compromising its specificity.
]]>Pathogens doi: 10.3390/pathogens13030245
Authors: Anil Baniya Connor J. Goldy Jiranun Ardpairin Perla Achi Yu Wei Chang Rose C. Adrianza Apichat Vitta Adler R. Dillman
The emergence of infectious diseases presents a significant global health, economic, and security risk. Climate change can unexpectedly lead to the spread of pathogens, vectors, or hosts into new areas, contributing to the rise of infectious diseases. Surveillance plays a crucial role in monitoring disease trends and implementing control strategies. In this study, we document the first discovery of Heterobilharzia americana, a parasitic schistosome of mammals and its intermediate hosts Galba cubensis and Galba humilis along the banks of the Colorado River in California. We conducted multiple samplings of snails from various locations in the region with a previous history of canine schistosomiasis. Nucleotide sequencing of the multiple regions of the snails’ and parasites’ DNA revealed the coexistence of G. cubensis and G. humilis, both infected with H. americana. Phylogenetic analyses further validate the presence of H. americana in California, suggesting a wider distribution than previously reported. Our findings have implications for public health, veterinary medicine, and biodiversity conservation, contributing to developing effective control strategies to prevent the spread of this emerging infectious disease.
]]>Pathogens doi: 10.3390/pathogens13030244
Authors: Giovanni Barco Zumama Khalid Alessandra Pulliero Claudio Angelinetta Ubaldo Prati Alberto Izzotti
The possible future emergence of new SARS-CoV-2 virus variants pushes the development of new chemoprophylaxis protocols complementary to the unspecific and specific immune-prophylaxis measures currently used. The SARS-CoV-2 virus is particularly sensitive to oxidation, due to the relevant positive electrical charge of its spike protein used as a ligand for target cells. The present study evaluated the safety and efficacy of a new oxidant preparation, liquid hyperoxygen (IOL), to neutralize the SARS-CoV-2 virus. IOL was incubated with throat swabs containing a human-type virus. The samples were then incubated with cells expressing the ACE2 receptor and, therefore, very sensitive to SARS-CoV-2 infection. The ability to neutralize SARS-CoV-2 was determined by assessing the amount of viral nucleic acid inside cells by PCR. The results obtained indicate that IOL, even at considerable dilutions, is capable, after incubation times of less than 30 min and even equal to 5 min, of completely inhibiting SARS-CoV-2 infection. This inhibitory effect has been shown to be due to the oxidizing capacity of the IOL. This oxidizing capacity is exerted towards the virus but does not damage eukaryotic cells either in the in vitro or in vivo skin models. Obtained results indicate that the use of IOL, a hydrophilic liquid mixture saturated with highly reactive oxygen and nitrogen species, is a new powerful, safe, and effective tool for preventing possible future outbreaks of the COVID-19 disease.
]]>Pathogens doi: 10.3390/pathogens13030243
Authors: Sofian Abdul-Nasir Hyungdon Lee Md. Habibur Rahman Johny Bajgai Kyu-Jae Lee Cheol-Su Kim Soo-Ki Kim
Cervical and prostate cancer account for 7.1 and 7.3 deaths per 100,000 people globally in 2022. These rates increased significantly to 17.6 and 17.3 in Africa, respectively, making them the second and third leading cause of cancer deaths in Africa, only surpassed by breast cancer. The human papillomavirus is the prime risk factor for cervical cancer infection. On the other hand, prostate cancer risks include ageing, genetics, race, geography, and family history. However, these factors alone cannot account for the high mortality rate in Africa, which is more than twice the global mortality rate for the two cancers. We searched PubMed, Embase, Scopus, and Web of Science to select relevant articles using keywords related to microorganisms involved in cervical and prostate cancer and the impact of poor healthcare systems on the mortality rates of these two cancers in Africa by carrying out a detailed synopsis of the studies on microbial agents involved and the contributory factors to the deteriorating healthcare system in Africa. It became apparent that the developed countries come first in terms of the prevalence of cervical and prostate cancer. However, more people per capita in Africa die from these cancers as compared to other continents. Also, microbial infections (bacterial or viral), especially sexually transmitted infections, cause inflammation, which triggers the pathogenesis and progression of these cancers among the African population; this has been linked to the region’s deficient health infrastructure, making it difficult for people with microbial infections to access healthcare and hence making infection control and prevention challenging. Taken together, untreated microbial infections, primarily sexually transmitted infections due to the deficient healthcare systems in Africa, are responsible for the high mortality rate of cervical and prostate cancer.
]]>Pathogens doi: 10.3390/pathogens13030242
Authors: Humberto Pires Luís Cardoso Ana Patrícia Lopes Maria da Conceição Fontes Sérgio Santos-Silva Manuela Matos Cristina Pintado Natália Roque Leonardo Filipe Fonseca Inês Morgado Ana Sofia Dias Luís Figueira Ana Cristina Matos João Rodrigo Mesquita Ana Cláudia Coelho
Between 2016 and 2023, a cross-sectional study was conducted in the central region of Portugal in order to better understand the epidemiology and public health risks resulting from the handling and consumption of game animals infected with Brucella spp. The seroprevalence and risk factors for Brucella spp. seropositivity were evaluated. Antibodies against Brucella spp. were determined using a commercial enzyme-linked immunosorbent assay (ELISA) according to the manufacturer’s instructions. Results showed that in the 650 serum samples collected from red deer (n = 298) and wild boars (n = 352) in Portugal, 21.7% (n = 141; 95% CI: 18.6–25.1%) tested positive. Wild boar had a significantly higher prevalence (35.5%; 95% CI: 30.5–40.8%) than red deer (5.4%, 95% CI: 3.1–8.6%; p ≤ 0.001). Risk factors for seropositivity were investigated using multivariable logistic regression models. The odds of being seropositive was 8.39 (95% CI: 4.75–14.84; p ≤ 0.001) times higher in wild boar than in red deer. Correlations between sex, age, body condition, and seropositivity could not be observed. The higher seroprevalence in wild boar suggests that this species may primarily contribute to the Brucella spp. ecology in central Portugal.
]]>Pathogens doi: 10.3390/pathogens13030241
Authors: Christophe Guillon Xavier Robert Patrice Gouet
Human T-cell Leukemia Virus type 1 (HTLV-1) is a human retrovirus responsible for leukaemia in 5 to 10% of infected individuals. Among the viral proteins, Tax has been described as directly involved in virus-induced leukemogenesis. Tax is therefore an interesting therapeutic target. However, its 3D structure is still unknown and this hampers the development of drug-design-based therapeutic strategies. Several algorithms are available that can be used to predict the structure of proteins, particularly with the recent appearance of artificial intelligence (AI)-driven pipelines. Here, we review how the structure of Tax is predicted by several algorithms using distinct modelling strategies. We discuss the consequences for the understanding of Tax structure/function relationship, and more generally for the use of structure models for modular and/or flexible proteins, which are frequent in retroviruses.
]]>Pathogens doi: 10.3390/pathogens13030240
Authors: Meagan D. Rippee-Brooks Wenzhe Wu Jianli Dong Miguel Pappolla Xiang Fang Xiaoyong Bao
Alzheimer’s Disease (AD), a progressive and debilitating condition, is reported to be the most common type of dementia, with at least 55 million people believed to be currently affected. Many causation hypotheses of AD exist, yet the intriguing link between viral infection and its possible contribution to the known etiology of AD has become an attractive focal point of research for the field and a challenging study task. In this review, we will explore the historical perspective and milestones that led the field to investigate the viral connection to AD. Specifically, several viruses such as Herpes Simplex Virus 1 (HSV-1), Zika virus (ZIKV), and severe cute respiratory syndrome coronavirus 2 (SARS-CoV-2), along with several others mentioned, include the various viruses presently considered within the field. We delve into the strong evidence implicating these viruses in the development of AD such as the lytic replication and axonal transport of HSV-1, the various mechanisms of ZIKV neurotropism through the human protein Musashi-1 (MSI1), and the spread of SARS-CoV-2 through the transfer of the virus through the BBB endothelial cells to glial cells and then to neurons via transsynaptic transfer. We will also explore beyond these mere associations by carefully analyzing the potential mechanisms by which these viruses may contribute to AD pathology. This includes but is not limited to direct neuronal infections, the dysregulation of immune responses, and the impact on protein processing (Aβ42 and hyperphosphorylated tau). Controversies and challenges of the virus–AD relationship emerge as we tease out these potential mechanisms. Looking forward, we emphasize future directions, such as distinct questions and proposed experimentations to explore, that the field should take to tackle the remaining unanswered questions and the glaring research gaps that persist. Overall, this review aims to provide a comprehensive survey of the past, present, and future of the potential link between viral infections and their association with AD development while encouraging further discussion.
]]>Pathogens doi: 10.3390/pathogens13030239
Authors: Evangelo Boumis Pierangelo Chinello Vincenzo Galati Simone Topino Francesca Gavaruzzi Stefania Cicalini
Brucellar endocarditis is a rare entity commonly described as a severe disease associated with high mortality and generally requiring valve surgery for cure. Right-sided endocarditis, a very uncommon presentation of brucellosis, may be associated with a better prognosis. We describe the case of a 72-year-old woman admitted to our institution with a persistent fever and multiple pulmonary infiltrates. Transthoracic echocardiography and serologic tests led to the diagnosis of brucellar tricuspid endocarditis. The patient responded favorably to antibiotic treatment alone and did not need surgery. Prolonged antibiotic therapy with a combination of drugs active on intracellular microorganisms in the absence of surgical treatment could be effective in brucellar tricuspid endocarditis when the valve is not severely damaged.
]]>Pathogens doi: 10.3390/pathogens13030238
Authors: Konstantinos V. Arsenopoulos Styliani Minoudi Isaia Symeonidou Alexandros Triantafyllidis George C. Fthenakis Elias Papadopoulos
The gastrointestinal nematode parasite Haemonchus spp. is one of the most pathogenic parasites of ruminants, due to its blood-sucking activity, which causes large economic losses in the ruminant industry. The latest epizootiological data recorded an increase in the infection, not only in Greece but also in other countries, mainly attributed to climatic changes. The study of the population structure and the investigation of the phylogenetic relationships of Haemonchus spp. are essential for the understanding of its biology and epizootiology to implement appropriate control and prevention strategies. In addition, the molecular approach allows the determination of evolutionary relationships between different species of this parasite, the diverse hosts they infect, as well as the different geographic compartments from which they originate. Therefore, the aim of the present study was to identify the species of the sympatric populations of the genus Haemonchus, a nematode parasite infecting ruminants (sheep, goats, cattle, and buffaloes) from different regions of Greece (continental and insular) using molecular methods. At the same time, an attempt was made to identify the possible subpopulations of Haemonchus spp. in Greece, to investigate their phylogenetic relationships, as well as to determine the genetic diversity of each population. A total of 288 worms of the genus Haemonchus were processed using molecular methods; of these, 96 were collected from sheep, 96 from goats, 48 from cattle, and finally, 48 from buffaloes. A fragment of 321 base pairs of the second internal transcribed spacer (ITS2) sequence of nuclear DNA was amplified for species identification, and, after basic local alignment search tool (Blast) analysis, it was revealed that they belonged to H. contortus. A fragment of 820 base pairs of subunit 4 of the nicotinamide dehydrogenase (ND4) gene of mitochondrial DNA was amplified for genetic diversity analysis. The Greek mitochondrial ND4 sequences of H. contortus were classified into 140 haplotypes, and the values of the average nucleotide and haplotype diversity were lower compared to the respective values derived from Italy, Malaysia, the USA, and China. The phylogenetic analysis of the ND4 gene revealed a clear grouping of the Greek haplotypes when compared with Asian ones, and, at the same time, there was no profound grouping of the same haplotypes with regard to their different hosts and geographical origin within different regions of Greece. The aforementioned findings confirmed that H. contortus prevails in our country and can infect all species of ruminants, without geographical boundaries, when the right conditions (i.e., common grazing) are created.
]]>Pathogens doi: 10.3390/pathogens13030237
Authors: Jaroslav Bzdil Soňa Šlosárková Petr Fleischer Monika Zouharová Ján Matiašovic
Gallibacterium anatis, recognized as a resident and opportunistic pathogen primarily in poultry, underwent investigation in unwell domestic mammals and birds. The study encompassed the mapping and comparison of G. anatis isolates, evaluation of their genetic diversity, and determination of their susceptibility to antimicrobials. A total of 11,908 clinical samples were analyzed using cultivation methods and MALDI-TOF. Whole-genome sequencing was performed on seven calf isolates and six hen isolates. Among mammals, G. anatis was exclusively detected in 22 young dairy calves, while among domestic birds, it was found in 35 individuals belonging to four species. Pathological observations in calves were predominantly localized in the digestive tract, whereas in birds, multi-organ infections and respiratory system infections were most prevalent. Distinct groups of genes were identified solely in calf isolates, and conversely, those unique to hen isolates were also recognized. Novel alleles in the multilocus sequence typing scheme genes and previously unidentified sequence types were observed in both calf and hen isolates. Antimicrobial susceptibility exhibited variation between bird and calf isolates. Notably, G. anatis isolates from calves exhibited disparities in genotype and phenotype compared to those from hens. Despite these distinctions, G. anatis isolates demonstrated the capability to induce septicemia in both species.
]]>Pathogens doi: 10.3390/pathogens13030236
Authors: Gaia Muroni Elisa Serra Giovanni Paolo Biggio Daniela Sanna Raffaele Cherchi Andrea Taras Simonetta Appino Cipriano Foxi Giovanna Masala Federica Loi Valentina Chisu
The members of the Chlamydiaceae family are important pathogens that infect a wide range of vertebrate hosts, including humans. Among them, Chlamydia psittaci, historically considered as an avian agent, has recently been identified in livestock, primarily sheep and cattle, but also in horses, with the infection being linked to reproductive disorders, such as abortion, absorption of embryos, stillbirth, and the birth of weak foals. Much less is known about chlamydial infections in the Sardinian equine population. This study aimed to identify the chlamydial diversity in genital samples from asymptomatic Sardinian horses. However, some horses had a previous history of reproductive disorders, i.e., abortion and infertility. A total of 60 horses (39 mares and 21 stallions) were opportunistically recruited from 17 equine farms in central-northern Sardinia. Vaginal and uterine swabs from mares and urethral swabs and seminal fluid from stallions were sampled for the presence of chlamydial DNA. Samples from environments where the horses lived were also tested for the detection of Chlamydia spp. Eight vaginal swabs (8/39; 20%), two uterine swabs (2/27; 7%), two seminal fluid samples (2/20; 10%), and one urethral swab (1/21; 4.7%) were found to be positive for Chlamydia spp. by PCR analysis. In addition, results from environmental samples showed the presence of Chlamydia spp. in three environmental swabs (3/8; 37.5%) and five water samples (5/16; 31.2%). Sequencing results revealed that strains here identified were 99–100% similar to members belonging to the Chlamydiaceae family, including C. abortus, C. psittaci, and uncultured Chlamydia genotypes. ompA species-specific PCR performed on samples was found to be positive after 16S rRNA amplification gave positive results for C. psittaci. These results reveal the first presence of C. psittaci in the genital tract of horses and in the environment in Sardinia and indicate that this pathogen could be the prevailing cause of infertility and abortion in the tested equines. However, these findings need further proof and highlight the importance of adopting a ‘One Health’ approach to control the presence of this zoonotic bacteria in domestic animals in order to understand its impact on people exposed to the infection risk.
]]>Pathogens doi: 10.3390/pathogens13030235
Authors: Francesco Nappi
Enterococcus faecalis is a bacterial pathogen that can cause opportunistic infections. Studies indicate that initial biofilm formation plays a crucial regulatory role in these infections, as well as in colonising and maintaining the gastrointestinal tract as a commensal member of the microbiome of most land animals. It has long been thought that vegetation of endocarditis resulting from bacterial attachment to the endocardial endothelium requires some pre-existing tissue damage, and in animal models of experimental endocarditis, mechanical valve damage is typically induced by cardiac catheterisation preceding infection. This section reviews historical and contemporary animal model studies that demonstrate the ability of E. faecalis to colonise the undamaged endovascular endothelial surface directly and produce robust microcolony biofilms encapsulated within a bacterially derived extracellular matrix. This report reviews both previous and current animal model studies demonstrating the resilient capacity of E. faecalis to colonise the undamaged endovascular endothelial surface directly and produce robust microcolony biofilms encapsulated in a bacterially derived extracellular matrix. The article also considers the morphological similarities when these biofilms develop on different host sites, such as when E. faecalis colonises the gastrointestinal epithelium as a commensal member of the common vertebrate microbiome, lurking in plain sight and transmitting systemic infection. These phenotypes may enable the organism to survive as an unrecognised infection in asymptomatic subjects, providing an infectious resource for subsequent clinical process of endocarditis.
]]>Pathogens doi: 10.3390/pathogens13030234
Authors: Anna Sala Valentina Pivetti Alessandra Vittorini Claudia Viggiano Francesca Castoldi Valentina Fabiano Gianluca Lista Francesco Cavigioli
Coagulase-negative staphylococci (CoNS) are reportedly responsible for 50–60% of bloodstream infections in very preterm (<1500 g) infants in neonatal intensive care units (NICUs). Staphylococcus capitis is an increasingly prevalent pathogen in the neonatal setting, frequently causing central-line-associated bloodstream infections (CLABSIs) that can be difficult to eradicate. Central venous catheter (CVC) removal versus in situ treatment with CoNS CLABSIs is a controversial treatment strategy with no clear consensus. We reviewed all S. capitis CLABSIs in our NICU between 2019 and 2022, focusing on the role of catheter removal in eradication. Among the 25 patients, 17 CVCs were removed after diagnosis, leading to a 76.5% eradication rate in this group. Three infants had a persistently positive blood culture after CVC substitution. A new catheter was then inserted after a 48 h washout period, resulting in resolution of the infection. Only two of the eight patients (25%) who retained their catheter after diagnosis achieved infection eradication with antibiotic therapy alone. When feasible, catheter removal seems to be the most effective strategy for eradicating S. capitis CLABSIs, sometimes even requiring a 48 h washout period before reinsertion. Further studies on this topic are needed to better standardize the management of this type of infection.
]]>Pathogens doi: 10.3390/pathogens13030233
Authors: Andrea Giammarino Nicolò Bellucci Letizia Angiolella
The study of pathogenicity and virulence of fungal strains, in vivo in the preclinical phase, is carried out through the use of animal models belonging to various classes of mammals (rodents, leproids, etc.). Although animals are functionally more similar to humans, these studies have some limitations in terms of ethics (animal suffering), user-friendliness, cost-effectiveness, timing (physiological response time) and logistics (need for adequately equipped laboratories). A good in vivo model must possess some optimal characteristics to be used, such as rapid growth, small size and short life cycle. For this reason, insects, such as Galleria mellonella (Lepidoptera), Drosophila melanogaster (Diptera) and Bombyx mori (Lepidoptera), have been widely used as alternative non-mammalian models. Due to their simplicity of use and low cost, the larvae of G. mellonella represent an optimal model above all to evaluate the virulence of fungal pathogens and the use of antifungal treatments (either single or in combination with biologically active compounds). A further advantage is also represented by their simple neuronal system limiting the suffering of the animal itself, their ability to survive at near-body ambient temperatures as well as the expression of proteins able to recognise combined pathogens following the three R principles (replacement, refinement and reduction). This review aims to assess the validity as well as the advantages and disadvantages of replacing mammalian classes with G. mellonella as an in vivo study model for preclinical experimentation.
]]>Pathogens doi: 10.3390/pathogens13030232
Authors: Kazuki Nagai Wataru Fujii Junya Yamagishi Chizu Sanjoba Yasuyuki Goto
Visceral leishmaniasis (VL) is an infectious disease caused by parasitic protozoa of the genus Leishmania and manifests clinical symptoms such as splenomegaly, hepatomegaly, anemia, and fever. It has previously been shown that B-cell-activating factor (BAFF) is involved in splenomegaly during VL. Although BAFF is known to be expressed by a variety of cells, the mechanism of elevated BAFF expression in VL is not clear. In this study, we aimed to identify BAFF-producing cells in the spleens of mice infected with Leishmania donovani. Splenocytes of L. donovani-infected mice showed elevated BAFF expression compared to that of naive mice. In the infected spleen, the number of both CD11b+ and F4/80+ cells increased, and the major BAFF-producing cells were CD11b+ cells, which did not serve as host cells of Leishmania. Immunohistochemical/immunofluorescent staining of spleens of infected mice revealed that the increased CD11b+ cells were primarily MRP14+ mononuclear cells. Together, these results suggest the increased BAFF expression in the spleen of L. donovani-infected mice involves a recruitment of inflammatory macrophages distinct from host macrophages for the parasites.
]]>Pathogens doi: 10.3390/pathogens13030231
Authors: Andreea Mădălina Panciu Cristina Alexandra Cheran Eliza Daniela Militaru Claudia Doina Rîciu Adriana Hristea
Background: Tick-borne encephalitis (TBE) is a disease with mandatory declaration in the EU since 2012. Information regarding the seroprevalence of the disease across Romania is limited, and only sporadic cases are rarely reported. We aimed to identify new areas of TBEV infection in different counties of Romania. Methods: We conducted a serosurvey assessing the immune response to TBEV infection in adult populations from rural areas in different counties of the country. Seropositivity was defined by a positive TBEV IgM/IgG ELISA test and confirmed by serum neutralization. Results: We collected 1116 samples from 15 different localities in 10 counties (divided into endemic/border/non-endemic counties) across Romania. Overall, 26 (2.3%) of the samples were tested positive using the TBEV ELISA assay in six counties. In those counties, 3.7% of sera were positive, varying from 1.4% to 6.9% per county. After performing the neutralization assay, seven (0.6%) samples were confirmed positive, interestingly all from one site in Sibiu County, where the seroprevalence was 9.7%. Conclusions: The identification of positive serum samples in serosurveys appears to rely on the discovery of TBEV microfoci. Further serological surveys should be conducted in Romania, especially after the identification of positive TBEV patients presenting for medical care.
]]>Pathogens doi: 10.3390/pathogens13030230
Authors: Shanrui Wu Ru Jia Ying Wang Jie Li Yisong Li Lan Wang Yani Wang Chao Liu Elena M. Jia Yihua Wang Guogang Zhang Jie Liu
Campylobacter species, especially C. jejuni and C. coli, are the main zoonotic bacteria causing human gastroenteritis. A variety of Campylobacter species has been reported in wild birds, posing a potential avian–human transmission pathway. Currently, there has been little surveillance data on Campylobacter carriage in migratory birds in China. In the current work, fresh fecal droppings from individual migratory birds were collected at four bird wintering/stopover sites in China from May 2020 to March 2021. Nucleic acid was extracted and tested for Campylobacter with PCR-based methods. Overall, 73.8% (329/446) of the samples were positive for Campylobacter, demonstrating location and bird host specificity. Further speciation revealed the presence of C. jejuni, C. coli, C. lari, C. volucris, and an uncharacterized species, which all harbored a variety of virulence factors. Phylogenetic analysis performed on concatenated 16S rRNA-atpA-groEL genes elucidated their genetic relationship, demonstrating both inter- and intra-species diversity. The wide distribution and high diversity of Campylobacter spp. detected in migratory birds in China indicated potential transmission across territories. The existence of virulence factors in all of these species highlighted their public health importance and the necessity of monitoring and controlling Campylobacter and other pathogens carried by migratory birds.
]]>Pathogens doi: 10.3390/pathogens13030229
Authors: Idris Nasir Abdullahi Carmen Lozano Carmen González-Azcona Myriam Zarazaga Carmen Torres
Coagulase-negative staphylococci (CoNS) species in healthy dogs and their owners could be transferred between these hosts and carry diverse antimicrobial resistance (AMR) genes of public health concern. This study determined the frequency, diversity, and AMR genes of nasal CoNS from healthy dogs and in-contact people as well as the rate of intra-household (between healthy dogs and dog-owners) transmission of CoNS. Nasal samples were collected and processed from 34 dogs and 41 humans from 27 households, and CoNS identification was done by MALDI-TOF-MS. The AMR determinants and genetic lineages were determined by PCR/sequencing. A total of 216 CoNS isolates were initially obtained and identified, and the AMR phenotypes were determined. From these, 130 non-repetitive CoNS were selected (one isolate of each species per sample or more than one if they presented different AMR phenotypes) and further characterized. The predominant species from dog carriers were S. epidermidis (26.5%), S. hominis (8.8%), and S. cohnii (8.8%), whereas in the human carriers, the predominant ones were S. epidermidis (80.4%), S. lugdunensis (9.8%), and S. hominis (9.8%). Intra-host species diversity (>one CoNS species) was detected in 37.5% of dogs and 21.6% of dog-owners. Conversely, 50% of dogs and 70.3% of dog-owners had intra-species AMR diversity (2–4 AMR-CoNS profiles). About 20% were susceptible to all antimicrobial agents tested, 31.5% displayed a multidrug resistance phenotype, and 17.4% were mecA-positive, located in SCCmec type V (24.2%), III (18.1%), IVc (12.1%), and II (6.1%). The other mec-A positive CoNS isolates (39.5%) had non-typeable SCCmec. The highest AMR rates were found against erythromycin (32.3%/mph(C), msr(A)) and mupirocin (20.8%/mupA), but the resistance rates for other antimicrobial agents were <10% each. Remarkably, one linezolid-resistant S. epidermidis-ST35 isolate was identified and mediated by four amino acid substitutions in L3 and one in L4 ribosomal proteins. Dogs and dog-owners as carriers of S. epidermidis with similar AMR patterns and genetic lineages (ST59, ST61, ST166 and ST278) were detected in four households (14.8%). Diverse CoNS carriage and moderate level of AMR were obtained from this study. The detection of CoNS carrying diverse SCCmec elements and intra-species AMR diversity highlights the roles of dog ownership in the potential transmission of antimicrobial-resistant CoNS in either direction.
]]>Pathogens doi: 10.3390/pathogens13030228
Authors: Jade Lawrence Paul Barrow Neil Foster
Clostridioides (Clostridium) difficile is an enteric pathogen of several mammalian species including man, frequently involving nosocomial resurgence, following oral administration of broad-spectrum antibiotics, but also with human-to-human infection occurring, and neonatal pigs with zoonotic transmission. To date, the immune response to C. difficile has mostly focused on neutrophils and cytokine/chemokines, particularly in human infection. The neonatal pig is now recognized as a valuable model for human infection. We show that porcine monocytes respond to C. difficile differently compared with many other bacterial infections. Infection of porcine monocytes with human C. difficile strains CD630 (Ribotype 078) or R20291 (Ribotype 027) for 3 or 24 h post-infection (pi) resulted in a lack of oxidative burst or nitrite ion production when compared to uninfected controls (p > 0.05). The survival dynamics of both CD630 and R20291 in monocytes were similar with intracellular bacterial numbers being similar at 3 h pi and 24 h pi (p > 0.05). However, we show that porcine monocytes entrap C. difficile via extracellular DNA traps. This process began as early as 3 h pi, and at 24 h pi the nuclei appeared to be depleted of DNA, although extracellular DNA was associated with the cell membrane. Our preliminary study also suggests that entrapment of C. difficile by extracellular DNA may occur via a process of monocyte etosis.
]]>Pathogens doi: 10.3390/pathogens13030227
Authors: Birgit Arnholdt-Schmitt Debabrata Sircar Shahid Aziz Thais Andrade Germano Karine Leitão Lima Thiers Carlos Noceda Revuru Bharadwaj Gunasekaran Mohanapriya José Hélio Costa
Xylella fastidiosa (Xf) is a global bacterial threat for a diversity of plants, including olive trees. However, current understanding of host responses upon Xf-infection is limited to allow early disease prediction, diagnosis, and sustainable strategies for breeding on plant tolerance. Recently, we identified a major complex trait for early de novo programming, named CoV-MAC-TED, by comparing early transcriptome data during plant cell survival with SARS-CoV-2-infected human cells. This trait linked ROS/RNS balancing during first hours of stress perception with increased aerobic fermentation connected to alpha-tubulin-based cell restructuration and control of cell cycle progression. Furthermore, our group had advanced concepts and strategies for breeding on plant holobionts. Here, we studied tolerance against Xf-infection by applying a CoV-MAC-TED-related gene set to (1) progress proof-of-principles, (2) highlight the importance of individual host responses for knowledge gain, (3) benefit sustainable production of Xf-threatened olive, (4) stimulate new thinking on principle roles of secondary metabolite synthesis and microbiota for system equilibration and, (5) advance functional marker development for resilience prediction including tolerance to Xf-infections. We performed hypothesis-driven complex analyses in an open access transcriptome of primary target xylem tissues of naturally Xf-infected olive trees of the Xf-tolerant cv. Leccino and the Xf-susceptible cv. Ogliarola. The results indicated that cyanide-mediated equilibration of oxygen-dependent respiration and carbon-stress alleviation by the help of increased glycolysis-driven aerobic fermentation paths and phenolic metabolism associate to tolerance against Xf. Furthermore, enhanced alternative oxidase (AOX) transcript levels through transcription Gleichschaltung linked to quinic acid synthesis appeared as promising trait for functional marker development. Moreover, the results support the idea that fungal endophytes strengthen Xf-susceptible genotypes, which lack efficient AOX functionality. Overall, this proof-of-principles approach supports the idea that efficient regulation of the multi-functional AOX gene family can assist selection on multiple-resilience, which integrates Xf-tolerance, and stimulates future validation across diverse systems.
]]>Pathogens doi: 10.3390/pathogens13030226
Authors: Giovanni Di Guardo
An interesting article recently published in Science Translational Medicine reports a variable risk of persistent COVID-19 among patients affected by different immunodeficiency conditions [...]
]]>Pathogens doi: 10.3390/pathogens13030225
Authors: Ming Z. Fan Sung Woo Kim
Global pig production contributes to about 35% of the world’s meat production and consumption [...]
]]>Pathogens doi: 10.3390/pathogens13030224
Authors: Roland W. Sutter Martin Eisenhawer Natalia A. Molodecky Harish Verma Hiromasa Okayasu
Inactivated poliovirus vaccine (IPV), available since 1955, became the first vaccine to be used to protect against poliomyelitis. While the immunogenicity of IPV to prevent paralytic poliomyelitis continues to be irrefutable, its requirement for strong containment (due to large quantities of live virus used in the manufacturing process), perceived lack of ability to induce intestinal mucosal immunity, high cost and increased complexity to administer compared to oral polio vaccine (OPV), have limited its use in the global efforts to eradicate poliomyelitis. In order to harvest the full potential of IPV, a program of work has been carried out by the Global Polio Eradication Initiative (GPEI) over the past two decades that has focused on: (1) increasing the scientific knowledge base of IPV; (2) translating new insights and evidence into programmatic action; (3) expanding the IPV manufacturing infrastructure for global demand; and (4) continuing to pursue an ambitious research program to develop more immunogenic and safer-to-produce vaccines. While the knowledge base of IPV continues to expand, further research and product development are necessary to ensure that the program priorities are met (e.g., non-infectious production through virus-like particles, non-transmissible vaccine inducing humoral and intestinal mucosal immunity and new methods for house-to-house administration through micro-needle patches and jet injectors), the discussions have largely moved from whether to how to use this vaccine most effectively. In this review, we summarize recent developments on expanding the science base of IPV and provide insight into policy development and the expansion of IPV manufacturing and production, and finally we provide an update on the current priorities.
]]>Pathogens doi: 10.3390/pathogens13030223
Authors: Benjamin Lee Md Abdul Kader Masud Alam Dorothy M. Dickson Patrick Harvey E. Ross Colgate Mami Taniuchi William A. Petri Rashidul Haque Beth D. Kirkpatrick
The infant non-secretor histoblood group antigen phenotype is associated with reduced risk of symptomatic rotavirus diarrhea, one of the leading global causes of severe pediatric diarrheal disease and mortality. However, little is known regarding the role of secretor status in asymptomatic rotavirus infections. Therefore, we performed a nested case–control study within a birth cohort study previously conducted in Dhaka, Bangladesh, to determine the association between infant secretor phenotype and the odds of asymptomatic rotavirus infection, in addition to the risk of rotavirus diarrhea, in unvaccinated infants. In the parent cohort, infants were enrolled in the first week of life and followed through the first two years of life with multiple clinic visits and active surveillance for diarrheal illness. Secretor phenotyping was performed on saliva. Eleven surveillance stools collected over the first year of life were tested for rotavirus by real-time RT-PCR, followed by conventional PCR and amplicon sequencing to identify the infecting P-type of positive specimens. Similar to findings for symptomatic diarrhea, infant non-secretors experienced significantly fewer primary episodes of asymptomatic rotavirus infection through the first year of life in a likely rotavirus P-genotype-dependent manner. These data suggest that non-secretors experienced reduced risk from rotavirus due to decreased susceptibility to infection rather than reduced infection severity.
]]>Pathogens doi: 10.3390/pathogens13030222
Authors: Caio Graco Zeppelini Ianei de Oliveira Carneiro Poliana Mascarenhas de Abreu Ann Katelynn Linder Romulo Romeu Nóbrega Alves Federico Costa
The practice of consuming wild fauna in Brazil is both culturally and socioeconomically questionable. Wild animals and their byproducts are sought for nutritional, medicinal, and/or supernatural reasons, with some taxa (e.g., songbirds) being kept as pets. This practice is concentrated in traditional and rural communities, as well as the rural exodus populations in large urban centers, maintained both by cultural preferences and for their role in food safety in part of the rural exodus community. A total of 564 taxa are known to be sold in wet markets in Brazil, with birds, fish, and mammals being the most commonly listed. There is great zoonotic outbreak potential in this consumption chain given the diversity of species involved (with several listed being known reservoirs of zoonotic pathogens), invasion of wild environments for hunting, unsanitary processing of carcasses, and consumption of most/all biotopes of the animal, as well as the creation of favorable conditions to cross-species pathogen transmission. Given its socioeconomic situation and the global trends in disease emergence, there is a risk of the future emergence of a Public Health Emergency of International Concern in Brazil through wildlife consumption.
]]>Pathogens doi: 10.3390/pathogens13030221
Authors: Minxiu Zhang Jianqi Liao Zhixun Xie Yanfang Zhang Sisi Luo Meng Li Liji Xie Qing Fan Tingting Zeng Jiaoling Huang Sheng Wang
Chicken parvovirus (ChPV) infection can cause runting-stunting syndrome (RSS) in chickens. There is currently no commercially available vaccine for controlling ChPV, and ChPV infection in chickens is widespread globally. The rapid detection of ChPV is crucial for promptly capturing epidemiological data on ChPV. Two monoclonal antibodies (mAbs), 1B12 and 2B2, against the ChPV NS1 protein were generated. A double-antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA) was developed for detecting ChPV based on the mAb 1B12 and an anti-chicken polyclonal antibody against the ChPV NS1 protein. The detection limit for the ChPV recombinant pET32a-NS1 protein was approximately 31.2 ng/mL. A total of 192 throat and cloaca swab samples were analyzed for ChPV by the established DAS-ELISA and nested PCR methods. The concordance rate between the DAS-ELISA and the nested PCR method was 89.1%. The DAS-ELISA can detect the ChPV antigen without any cross-reaction with FAdV-4, FAdV-1, NDV, AIV, MS, CIAV, aMPV, EDSV, IBV, or AGV2. The method also has high repeatability, with a coefficient of variation (CV) of less than 5%. These findings indicate that the DAS-ELISA exhibits high accuracy, good sensitivity, and specificity, making it suitable for viral detection, field surveillance, and epidemiological studies.
]]>Pathogens doi: 10.3390/pathogens13030220
Authors: Fermín García-Muñoz Rodrigo Lourdes Urquía Martí Marta Siguero Onrubia Moreyba Borges Luján Gloria Galán Henríquez Desiderio Reyes Suárez
The lung microbiota is a complex community of microorganisms that colonize the respiratory tract of individuals from, or even before, birth. Although the lungs were traditionally believed to be sterile, recent research has shown that there is a diversity of bacterial species in the respiratory system. Knowledge about the lung microbiota in newborns and its relationship with bacterial infections is of vital importance to understand the pathogenesis of respiratory diseases in neonatal patients undergoing mechanical ventilation. In this article, the current evidence on the composition of the lung microbiota in newborns will be reviewed, as well as the risks that an altered microbiota can impose on premature newborns. Although advances in neonatal intensive care units have significantly improved the survival rate of preterm infants, the diagnosis and treatment of ventilator-associated pneumonia has not progressed in recent decades. Avoiding dysbiosis caused by inappropriate use of antibiotics around birth, as well as avoiding intubation of patients or promoting early removal of endotracheal tubes, are among the most important preventive measures for ventilator-associated pneumonia. The potential benefit of probiotics and prebiotics in preventing infectious, allergic or metabolic complications in the short or long term is not clearly established and constitutes a very important field of research in perinatal medicine.
]]>Pathogens doi: 10.3390/pathogens13030219
Authors: Daniela D. Moré Katherine N. Baker Smriti Shringi Reginaldo G. Bastos Donal O’Toole Gaetano Donofrio Cristina W. Cunha
Ovine herpesvirus 2 (OvHV-2) and bovine herpesvirus 4 (BoHV-4) are gamma herpesviruses that belong to the genera Macavirus and Rhadinovirus, respectively. As with all herpesviruses, both OvHV-2 and BoHV-4 express glycoprotein B (gB), which plays an essential role in the infection of host cells. In that context, it has been demonstrated that a BoHV-4 gB-null mutant is unable to infect host cells. In this study, we used homologous recombination to insert OvHV-2 ORF 8, encoding gB, into the BoHV-4 gB-null mutant genome, creating a chimeric BoHV-4 virus carrying and expressing OvHV-2 gB (BoHV-4∆gB/OvHV-2-gB) that was infectious and able to replicate in vitro. We then evaluated BoHV-4∆gB/OvHV-2-gB as a potential vaccine candidate for sheep-associated malignant catarrhal fever (SA-MCF), a fatal disease of ungulates caused by OvHV-2. Using rabbits as a laboratory model for MCF, we assessed the safety, immunogenicity, and efficacy of BoHV-4∆gB/OvHV-2-gB in an immunization/challenge trial. The results showed that while BoHV-4∆gB/OvHV-2-gB was safe and induced OvHV-2 gB-specific humoral immune responses, immunization conferred only 28.5% protection upon challenge with OvHV-2. Therefore, future studies should focus on alternative strategies to express OvHV-2 proteins to develop an effective vaccine against SA-MCF.
]]>Pathogens doi: 10.3390/pathogens13030216
Authors: Zhongzhou Yang Kanru Cai Yuqi Liao Wei-Chen Wu Li Xing Minxuan Hu Jiali Ren Jieyun Zhang Xiuyun Zhu Ke Yuan Shunyao Wang Hui Huang Chunhui Yang Mingxia Zhang Mang Shi Hongzhou Lu
Between 7 December 2022 and 28 February 2023, China experienced a new wave of COVID-19 that swept across the entire country and resulted in an increasing amount of respiratory infections and hospitalizations. The purpose of this study is to reveal the intensity and composition of coinfecting microbial agents. In total, 196 inpatients were recruited from The Third People’s Hospital of Shenzhen, and 169 respiratory and 73 blood samples were collected for metagenomic next-generation sequencing. The total “Infectome” was characterized and compared across different groups defined by the SARS-CoV-2 detection status, age groups, and severity of disease. Our results revealed a total of 22 species of pathogenic microbes (4 viruses, 13 bacteria, and 5 fungi), and more were discovered in the respiratory tract than in blood. The diversity of the total infectome was highly distinguished between respiratory and blood samples, and it was generally higher in patients that were SARS-CoV-2-positive, older in age, and with more severe disease. At the individual pathogen level, HSV-1 seemed to be the major contributor to these differences observed in the overall comparisons. Collectively, this study reveals the highly complex respiratory infectome and high-intensity coinfection in patients admitted to the hospital during the period of the 2023 COVID-19 pandemic in China.
]]>Pathogens doi: 10.3390/pathogens13030217
Authors: Tuomas Hintikka Maria A. Andersson Taina Lundell Tamás Marik László Kredics Raimo Mikkola Magnus C. Andersson Jarek Kurnitski Heidi Salonen
It is controversial how useful bioassays are for identifying the in vivo toxicity of hazardous environmental exposures. In this study, fruiting bodies of forest mushrooms (n = 46), indoor mold colonies (n = 412), fungal secondary metabolites (n = 18), xenobiotic chemicals such as biocides and detergents (n = 6), and methanol extracts of indoor dusts from urban buildings (n = 26) were screened with two different bioactivity assays: boar sperm motility inhibition (BSMI) and inhibition of cell proliferation (ICP) tests. For the forest mushrooms, the toxicity testing result was positive for 100% of poisonous-classified species, 69% of non-edible-classified species, and 18% of edible-classified species. Colonies of 21 isolates of Ascomycota mold fungal species previously isolated from water-damaged buildings proved to be toxic in the tests. Out of the fungal metabolites and xenobiotic chemicals, 94% and 100% were toxic, respectively. Out of the indoor dusts from moldy-classified houses (n = 12) and from dry, mold-free houses (n = 14), 50% and 57% were toxic, respectively. The bioassay tests, however, could not differentiate the samples from indoor dusts of moldy-classified buildings from those from the mold-free buildings. Xenobiotic chemicals and indoor dusts were more toxic in the BSMI assay than in the ICP assay, whereas the opposite results were obtained with the Ascomycota mold colonies and fungal secondary metabolites. The tests recognized unknown methanol-soluble thermoresistant substances in indoor settled dusts. Toxic indoor dusts may indicate a harmful exposure, regardless of whether the toxicity is due to xenobiotic chemicals or microbial metabolites.
]]>Pathogens doi: 10.3390/pathogens13030218
Authors: Pedro Tadao Hamamoto Filho Luiz Fernando Norcia Agnès Fleury Marco Antônio Zanini
Neurocysticercosis (NCC) is a common parasitic disease of the central nervous system (CNS) in low- and middle-income countries. The infection is pleomorphic, caused by the larval form of the cestode, Taenia solium, and part of the heterogeneity of its clinical presentations is associated with the localization of the parasite within the CNS. Changes in the current epidemiological trends of NCC indicate that extra-parenchymal NCC is proportionally becoming more frequent. Extraparenchymal NCC is commonly accompanied by raised intracranial hypertension due to hydrocephalus, which is an emergency requiring cyst extirpation by surgical intervention to relieve the symptoms. Although less frequent, parenchymal cysts may also reach giant sizes requiring urgent surgical treatment. Finally, there is an advancement in the comprehension of the association between NCC and epilepsy—and patients with drug-resistant seizures are candidates for surgical treatment. In this narrative review, we summarize the present state of knowledge to update the current trends in the role of surgery in the treatment of NCC.
]]>Pathogens doi: 10.3390/pathogens13030215
Authors: Michele Nardone Dario Di Stasio Alberta Lucchese Daniele Gentili Giulia Cattabianchi Carlo Signorelli Pierangelo Sarchi Giovanna Pulcrano Valentino Lembo Paola Maria Pirola Dorina Lauritano Francesco Carinci
Hepatitis C virus (HCV) infection is a significant public health problem affecting 58 million people worldwide, including 3.9 million in Europe. Many of these infections go undiagnosed because chronic infection is often asymptomatic. This observational cohort study presents a detailed examination of hepatitis C virus epidemiology in Lombardia (Italy) and was conducted within the ASST “Melegnano e della Martesana”. The study involved comprehensive HCV screening of 3290 patients accessing the collection points and/or hospitalized in the facilities of the ASST from 20 May 2022 to 13 April 2023. Screening was conducted using serological assays. The prevalence of anti-HCV-positive patients (HCV-Ab) and then HCV-positive patients (RNA) was calculated. Chi-square tests examined the associations between continuous and categorical variables. Logistic regression was used to evaluate the influence of demographic and geographic variables as predictors of HCV positivity. The study revealed an overall HCV-Ab prevalence of 0.912% (CI (0.59–1.24%)) in the examined cohort, of whom 15.15% (two females and three males) were positive for HCV RNA. The prevalence of HCV RNA positivity was 0.152% (CI (0.05–0.35%)). Sex disparity was evident, with male patients exhibiting a higher prevalence compared to females, confirmed by logistic regression (0.0147 vs. 0.0061–OR = 2.44; CI (0.0059–0.0124)). Age stratification indicated an ascending trend in prevalence with age, peaking at 1.35% in individuals aged over 50. These findings underscore the critical need for targeted HCV screening, contributing valuable insights to the global epidemiology of HCV in the era of DAAs.
]]>Pathogens doi: 10.3390/pathogens13030214
Authors: Kholood K. Altassan Cory W. Morin Jeremy J. Hess
The first case of dengue fever (DF) in Saudi Arabia appeared in 1993 but by 2022, DF incidence was 11 per 100,000 people. Climatologic and population factors, such as the annual Hajj, likely contribute to DF’s epidemiology in Saudi Arabia. In this study, we assess the impact of these variables on the DF burden of disease in Saudi Arabia and we attempt to create robust DF predictive models. Using 10 years of DF, weather, and pilgrimage data, we conducted a bivariate analysis investigating the role of weather and pilgrimage variables on DF incidence. We also compared the abilities of three different predictive models. Amongst weather variables, temperature and humidity had the strongest associations with DF incidence, while rainfall showed little to no significant relationship. Pilgrimage variables did not have strong associations with DF incidence. The random forest model had the highest predictive ability (R2 = 0.62) when previous DF data were withheld, and the ARIMA model was the best (R2 = 0.78) when previous DF data were incorporated. We found that a nonlinear machine-learning model incorporating temperature and humidity variables had the best prediction accuracy for DF, regardless of the availability of previous DF data. This finding can inform DF early warning systems and preparedness in Saudi Arabia.
]]>Pathogens doi: 10.3390/pathogens13030213
Authors: Trong-Nhat Phan Hyeryon Lee Kyung-Hwa Baek Joo Hwan No
The protozoan parasite Leishmania donovani is the causative agent of visceral leishmaniasis (VL), a potentially fatal disease if left untreated. Given the limitations of current therapies, there is an urgent need for new, safe, and effective drugs. To discover novel antileishmanial compounds from previously unexplored chemical spaces, we conducted a high-throughput screening (HTS) of 2562 natural compounds, assessing their activity against L. donovani promastigotes and intracellular amastigotes. Utilizing the criteria of ≥70% parasite growth inhibition and ≥70% host cell (THP-1) viability, we selected 100 inhibitors for half-maximal inhibitory concentration (IC50) value determination. Twenty-six compounds showed activities in both forms of Leishmania with a selectivity index of over 3. Clustering analysis resulted in four chemical clusters with scaffolds of lycorine (cluster 1), 5-hydroxy-9,10-dihydro-4H,8H-pyrano[2,3-f]chromene-4,8-dione (cluster 2), and semi-synthetic derivatives of ansamycin macrolide (cluster 4). The enantiomer of lycorine, BMD-NP-00820, showed the highest anti-amastigote activity with an IC50 value of 1.74 ± 0.27 μM and a selectivity index (SI) > 29. In cluster 3, the most potent compound had an IC50 value of 2.20 ± 0.29 μM with an SI > 23, whereas in cluster 4, with compounds structurally similar to the tuberculosis drug rifapentine, BMD-NP-02085 had an IC50 value of 1.76 ± 0.28 μM, but the SI value was 7.5. Taken together, the natural products identified from this study are a potential source for the discovery of antileishmanial chemotypes for further development.
]]>Pathogens doi: 10.3390/pathogens13030212
Authors: Rosa González-Vázquez María Guadalupe Córdova-Espinoza Alejandro Escamilla-Gutiérrez María del Rocío Herrera-Cuevas Raquel González-Vázquez Ana Laura Esquivel-Campos Laura López-Pelcastre Wendoline Torres-Cubillas Lino Mayorga-Reyes Felipe Mendoza-Pérez María Angélica Gutiérrez-Nava Silvia Giono-Cerezo
Methicillin-resistant (MR) Staphylococcus aureus (SA) and others, except for Staphylococcus aureus (SOSA), are common in healthcare-associated infections. SOSA encompass largely coagulase-negative staphylococci, including coagulase-positive staphylococcal species. Biofilm formation is encoded by the icaADBC operon and is involved in virulence. mecA encodes an additional penicillin-binding protein (PBP), PBP2a, that avoids the arrival of β-lactams at the target, found in the staphylococcal cassette chromosome mec (SCCmec). This work aims to detect mecA, the bap gene, the icaADBC operon, and types of SCCmec associated to biofilm in MRSA and SOSA strains. A total of 46% (37/80) of the strains were S. aureus, 44% (35/80) S. epidermidis, 5% (4/80) S. haemolyticus, 2.5% (2/80) S. hominis, 1.25% (1/80) S. intermedius, and 1.25% (1/80) S. saprophyticus. A total of 85% were MR, of which 95.5% showed mecA and 86.7% β-lactamase producers; thus, Staphylococcus may have more than one resistance mechanism. Healthcare-associated infection strains codified type I-III genes of SCCmec; types IV and V were associated to community-acquired strains (CA). Type II prevailed in MRSA mecA strains and type II and III in MRSOSA (methicillin-resistant staphylococci other than Staphylococcus aureus). The operon icaADBC was found in 24% of SA and 14% of SOSA; probably the arrangement of the operon, fork formation, and mutations influenced the variation. Methicillin resistance was mainly mediated by the mecA gene; however, there may be other mechanisms that also participate, since biofilm production is related to genes of the icaADBC operon and methicillin resistance was not associated with biofilm production. Therefore, it is necessary to strengthen surveillance to prevent the spread of these outbreaks both in the nosocomial environment and in the community.
]]>Pathogens doi: 10.3390/pathogens13030211
Authors: Dongyuan Wang Feng Zhu Jichun Wang Hongguang Ju Yongfeng Yan Shanyan Qi Yuping Ou Chengli Tian
In order to understand the pathogenicity differentiation of rice blast fungus (Pyricularia oryzae Cavara), a total of 206 isolates of P. oryzae were collected from three Japonica rice regions in Jilin Province, northeast China. Pathogenicity test showed that the reaction pattern of 25 monogenic differential varieties (MDVs) of rice (Oryza sativa L.) demonstrated a wide pathogenic diversity among the isolates. Those MDVs harbor 23 resistance (R) genes with the susceptible variety Lijiangxintuanheigu (LTH) as control. Virulent isolates of MDVs harboring R genes Pish, Pit, Pia, Pii, Pik-s, Pik, Pita (two lines), and Pita-2 (two lines) had high frequencies ranging from 80 to 100%, to MDVs harboring R genes Pib, Pi5(t), Pik-m, Pi1, Pik-h, Pik-p, Pi7(t), Piz, Piz-5, and Piz-t showed intermediate frequencies ranging from 40 to 80%, and to MDVs with R genes Pi3, Pi9(t), Pi12(t), Pi19(t) and Pi20(t) presented low frequencies ranging only from 0 to 40%. The U-i-k-z-ta pattern of race-named criteria categorized the 206 isolates into 175 races. Sub-unit U73 for Pib, i7 for Pi3 and Pi5(t), k177 for Pik-m/Pik-h/Pik-p, z17 for Pi9(t), and ta332 for Pi20(t) were crucial on pathogenic differences in regions. Twenty-seven standard differential blast isolates (SDBIs) were selected to characterize resistance in rice accessions. This study could help to build a durable identification system against blast in the Japonica rice area of northeast China and enhance our understanding of the differentiation and diversity of blast races in the world.
]]>Pathogens doi: 10.3390/pathogens13030210
Authors: Natalia Osten-Sacken Jutta Pikalo Peter Steinbach Mike Heddergott
The intracellular protozoan Toxoplasma gondii is distributed worldwide and infects many species of warm-blooded animals. Most mammals, including humans, can serve as intermediate hosts. This pathogen, with its zoonotic potential, causes toxoplasmosis, a condition that can range from subclinical to fatal in humans. It is therefore important to assess the occurrence of the pathogen, even if only indirectly through the detection of antibodies. Epidemiological data on the seroprevalence in wild animals, including invasive species, are rare in Poland. Therefore, we tested 197 wild raccoons (Procyon lotor) and 89 raccoon dogs (Nyctereutes procyonoides) from Zgorzelec County, southwestern Poland, for the presence of antibodies. Samples were collected between January 2019 and December 2020 and analysed using a commercial indirect modified agglutination test (MAT, cut-off 1:25). The statistical analysis revealed significant differences in seroprevalence between the two predatory species. Of the 197 surveyed raccoons, 96 (48.73%; 95% confidence interval (CI): 41.73–55.73%) tested positive, while 25 of the 89 raccoon dogs (28.09%; 95% CI: 18.70–37.48%) were positive. Regarding risk factors, body weight and sex influenced the presence of T. gondii antibodies in both the species, with a higher likelihood of seropositivity among heavier animals and females, respectively. For raccoon dogs, juveniles were more likely to be seropositive than adults at a given weight. Our results suggest that T. gondii infection is widespread in the regional raccoon and raccoon dog populations, indicating a high level of parasite circulation in the environment.
]]>Pathogens doi: 10.3390/pathogens13030209
Authors: María Liz Bobadilla Verónica Villagra Héctor Castro Marta von Horoch Soraya Araya Gerardo Deluca Vanessa Salete de Paula
Cervical cancer is a global health concern and ranks fourth among the most prevalent cancers in women worldwide. Human papillomavirus (HPV) infection is a known precursor of cervical cancer and preventive measures include prophylactic vaccines. This study focused on sexually active Paraguayan women aged 18–25 years, exploring the intersection of HPV vaccination and sexual behavior. Among 254 participants, 40.9% received the Gardasil-4 vaccine, with no significant differences in sexual behavior between the vaccinated and unvaccinated sexually active groups. However, a notable decrease in the prevalence of HPV among the vaccinated women highlights the efficacy of this vaccine in reducing infections. The prevalence of any HPV type was 37.5% in vaccinated participants compared to 56.7% in unvaccinated participants (p = 0.0026). High-risk HPV types showed a significant difference, with a prevalence of 26.0% in vaccinated women compared with 52.7% in unvaccinated women (p < 0.001). Although a potential decline in genital warts was observed among the vaccinated individuals, statistical significance (p = 0.0564) was not reached. Despite the challenges in achieving high vaccination coverage, the observed reduction in HPV prevalence underscores the importance of ongoing monitoring, healthcare professional recommendations, and comprehensive risk management. These findings contribute to dispelling concerns about HPV vaccination influencing sexual behavior, advocating further large-scale research to explore the impact of vaccines on various HPV types and potential cross-protection.
]]>Pathogens doi: 10.3390/pathogens13030208
Authors: Jeffrey J. Shaw Abhay Satoskar
There are rare individuals whose insatiable curiosity and boundless intellect propel them into multiple frontiers of science, leaving an indelible mark on the fields that they venture into [...]
]]>Pathogens doi: 10.3390/pathogens13030207
Authors: Maria Beatrice Valli Antonella Vulcano Martina Rueca Giulia Matusali Valentina Mazzotta Emanuele Nicastri Enrico Girardi Carla Fontana Andrea Antinori Fabrizio Maggi
The recent multi-country outbreak of the zoonotic monkeypox virus (MPXV) infection in humans without an epidemiological link with endemic areas has raised concerns about the route of transmission. Since the infection spread largely among men who have sex with men who, in most cases, presented primary lesions of the genital and oral mucosa, sexual transmission has been proposed. In the present study, we retrospectively evaluated specimens of vesicular lesions collected from the skin and genital tract of 35 patients (23 positive and 12 negative) presenting at our Institute for monkeypox (mpox) diagnosis by using a novel molecular syndromic vesicular virus panel (VVP) assay. All MPXV-positive samples but one was confirmed; however, the viral syndromic analysis revealed that 8.6% of them were coinfected with one or more viruses, and 17% had at least a virus different from the MPXV. The percentage of coinfections increased to more than 25% when nonviral pathogens, such as gonorrhea and syphilis, were also considered. These results show the usefulness of syndromic diagnosis in cases where MPXV is suspected (and vice versa) and at the same time highlight that the broader screening of sexually transmitted infections in the population with high-risk sexual behavior is critical to ensure a complete etiology and appropriate treatment.
]]>Pathogens doi: 10.3390/pathogens13030206
Authors: Natalia Gómez-Casanova Mª Nieves Gutiérrez-Zufiaurre Ana Mª Blázquez de Castro Juan Luis Muñoz-Bellido
Daptomycin is one of the last therapeutic resources for multidrug-resistant gram-positive bacteria. Despite its structural similarities with glycopeptides, its mechanisms of action and resistance are different and in some respects are not completely understood. Mutations in several genes have been associated with daptomycin resistance, especially in mprF, walkR, rpoB and rpoC, but their role and importance remain to be elucidated. We have studied mutations in 11 genes, which have been previously associated with daptomycin non-susceptibility, in nine daptomycin-non-susceptible Staphylococcus aureus clinical isolates (daptomycin MIC: >1 mg/L). Susceptibility to daptomycin, vancomycin, linezolid, oxacillin, telavancin and dalbavancin was studied. walkR, agrA, cls1, cls2, fakA, pnpA, clpP, prs, rpoB, rpoC and mprF were amplified by PCR and sequenced. The sequences were compared with the S. aureus ATCC 25923 complete genome (GenBank gi: 685631213) by using BLAST® software. We did not find any changes in walkR, pnpA, prs and clpP. All isolates excepting isolate MSa5 showed a high number of significant mutations (between 13 and 25 amino acid changes) in mprF. Most isolates also showed mutations in the rpo genes, the cls genes and fakA. Daptomycin non-susceptibility in S. aureus clinical isolates seems to be reached through different mutation combinations when compared to S. aureus ATCC 25293. Especially mprF and cls1 showed very high polymorphism in most isolates. Meanwhile, one isolate, MSa5, showed only single mutation in mprF (P314T).
]]>Pathogens doi: 10.3390/pathogens13030205
Authors: Kamenna Vutova Nina Yancheva-Petrova Rossitsa Tchipeva Valeri Velev
Visceral leishmaniasis (VL) is a severe endemic disease with a fatal outcome if left untreated. The symptoms of patients are diverse and atypical. Against the background of anemia and pancytopenia, the condition of the patients gradually worsens with marked cachexia. Through sharing our experience, we aim to draw attention to this deadly disease. Clinical and laboratory data for 58 patients with VL treated over a forty-five-year period are presented. The diagnosis was established within a duration of 1 to 28 months of illness. Continuous fever (38–42 °C), splenomegaly, hepatomegaly, severe anemia (decreased hemoglobin to lowest values of 31 g/L), leucopenia (lowest values of leucocytes et 0.5 g/L), and thrombocytopenia (reduced thrombocyte count to 29 g/L) were observed. The diagnosis was made on the basis of microscopic evidence of amastigote forms in bone marrow smears and serological tests. The patients were treated with Glucantime for 17 to 21 days. Relapses were observed in seven patients (12.1%) and fatal outcome was observed in two patients (3.5%) during treatment, who developed acute respiratory and cardiovascular failure. In Bulgaria, Visceral leishmaniasis is primarily endemic in the southern regions and should be suspected not only in patients who have returned from tropical and subtropical countries, but also in those who have not traveled abroad. The challenges associated with VL stem from delayed diagnosis of patients, as this disease remains unrecognized by physicians.
]]>Pathogens doi: 10.3390/pathogens13030204
Authors: Mary Nkongho Tanyitiku Graeme Nicholas Jon J. Sullivan Igor C. Njombissie Petcheu Stephen L. W. On
Background: Land snails are considered a delicacy in many countries in Europe and sub-Saharan Africa. However, the interaction of microbial pathogens with land snails may present a public health threat when handling and/or consuming snails. This study examines the survival of Escherichia coli in edible land snails in a model system. Methods: Well-studied Shigatoxigenic (STEC) and non-STEC strains were compared. Mature Helix spp. were experimentally fed with E. coli-inoculated oats for 48 h. The snail feces after inoculation were periodically sampled and cultured for a 30-day period and subjected to microbiological analyses. Results: The average rate of decline of the non-STEC strain CSH-62 in the feces of live snails was significantly (p < 0.05) faster than that of STEC ERL 06-2503. In addition, the viable population of E. coli ERL 06-2503 significantly (p < 0.05) persisted for a longer time in the intestine of land snails than E. coli CSH-62. Conclusion: The results showed that the viable population of the E. coli strains examined demonstrated first-order kinetics, and their survival (CFU/mL) appeared significantly (p < 0.05) dependent on the E. coli pathotype. In addition, the continuous enumeration of E. coli in snail faeces indicated that land snails could serve as a mode of transmission of microbial pathogens to susceptible hosts, including humans. Further research is recommended to better quantify the direct and indirect health risks of pathogen transmission by edible snails to humans.
]]>Pathogens doi: 10.3390/pathogens13030203
Authors: Aparna Dalvi Umair Ahmed Bargir Gita Natraj Ira Shah Manisha Madkaikar
The diagnosis and treatment of patients with mendelian susceptibility to mycobacterial disease (MSMD) pose consistent challenges due to the diverse infection spectrum observed in this population. Common clinical manifestations include Bacillus Calmette-Guérin vaccine (BCG) complications in countries where routine BCG vaccination is practiced, while in non-BCG-vaccinating countries, Non-Tuberculous Mycobacteria (NTM) is prevalent. In tuberculosis-endemic regions, Mycobacterium tuberculosis (MTB) has a high prevalence, along with other intracellular organisms. Isolating these organisms presents a significant challenge, and treatment is often initiated without confirming the specific species. This review primarily focuses on the methods and challenges associated with diagnosing and treating MSMD patients.
]]>Pathogens doi: 10.3390/pathogens13030202
Authors: Talita Adelino Maurício Lima Natália R. Guimarães Joilson Xavier Vagner Fonseca Luiz Marcelo R. Tomé Maira Alves Pereira Vanessa Ferreira Machado Luiz Carlos Junior Alcantara Felipe C. de Melo Iani Marta Giovanetti
This report provides a detailed overview of the resurgence of DENV-3 in the state of Minas Gerais, Brazil, which is a concerning scenario in the context of dengue, a mosquito-borne viral disease. Historically, Brazil has grappled with dengue epidemics caused primarily by the DENV-1 and DENV-2 serotypes. However, in 2023, a significant shift in this pattern was observed as DENV-3 made a notable resurgence. This resurgence was characterized by the increase in DENV-3 cases within the country and the region of the Americas. Given the absence of sustained DENV-3 circulation in Brazil in previous years, this situation poses a significant risk, making the population highly susceptible to a potential novel epidemic. In November 2023, a 31-year-old male patient in Belo Horizonte exhibited symptoms of acute febrile syndrome. Multiplex RT-qPCR using the Kit Molecular ZC D-Tipagem confirmed DENV-3 infection, suggesting a likely autochthonous case, as the patient reported no travel history. To promptly assess this resurgence, we applied the nanopore sequencing technology. This allowed for the rapid characterization of the initial DENV-3 case isolated in Minas Gerais in 2023, representing a 13-year interval since the serotype’s previous documented circulation in that state. This case report underscores the critical importance of proactive monitoring and the swift implementation of targeted control strategies to address the evolving dynamics of dengue, with a specific emphasis on the resurgence of DENV-3 in the state.
]]>Pathogens doi: 10.3390/pathogens13030201
Authors: Vered Shkalim Zemer Shai Ashkenazi Yoel Levinsky Yael Richenberg Eyal Jacobson Shay Nathanson Tzippy Shochat Shiri Kushnir Moriya Cohen Avner Herman Cohen
Urinary tract infections (UTIs) in childhood are common and are associated with considerable acute morbidity and long-term complications. The need for updated data to optimize empiric antibiotic therapy is crucial. We aimed to investigate the pathogens causing pediatric community acquired UTIs, their correlation with demographic characteristics, and trends in their antimicrobial resistance. This nationwide cross-sectional study included all 53,203 children (<18 years) diagnosed with UTI in community outpatient clinics in the following selected years: 2007, 2011, 2015, 2019 and 2021. Escherichia coli (E. coli) (82.1%) was the most common uropathogen, followed by Enterobacter, Klebsiella, Proteus, Pseudomonas, and Enterococcus species. The bacterial distribution displayed statistically significant (p < 0.0001) gender- and sector-specific patterns with a higher relative prevalence of non-E. coli UTI in Jewish and males. The rate of extended-spectrum beta-lactamase-positive E. coli increased substantially and significantly (p < 0.001) from only 6.1% in 2007 to 25.4% in 2021. Most non-E. coli uropathogens exhibited resistance to commonly used empiric antibiotics for UTIs in children. These findings are significant in guiding optimal empiric antibiotic treatment for pediatric community acquired UTIs. The resistance of uropathogens to antimicrobials is region- and time-dependent. Therefore, the periodic and local assessment of antibiotic resistance trends is essential to update guidelines and provide the most appropriate antibacterial therapy for children with UTIs.
]]>Pathogens doi: 10.3390/pathogens13030200
Authors: Elizabeth M. Quincer Lisa M. Cranmer Satoshi Kamidani
Prenatal maternal immunization is an effective tool to protect mothers and infants from poor health outcomes due to infectious diseases. We provide an overview of the rationale for the use of prenatal vaccines, discuss the immunologic environment of the maternal–fetal interface including the impact of maternal vaccines prenatally and subsequently on the infant’s immune response, and review vaccines currently recommended in pregnancy and landscape for the future of maternal vaccination. This review aims to provide an understanding of the recent history and progress made in the field and highlight the importance of continued research and development into new vaccines for pregnant populations.
]]>Pathogens doi: 10.3390/pathogens13030199
Authors: Augusto M. Carvalho Rúbia S. Costa Alexsandro Lago Olívia Bacellar Daniel P. Beiting Phillip Scott Lucas P. Carvalho Edgar M. Carvalho
The role of the immune response in the pathogenesis of cutaneous leishmaniasis (CL) due to Leishmania (Viannia) braziliensis is predominantly carried out via blood cells. Here, we evaluate whether cytokine production by peripheral blood mononuclear cells (PBMCs) reflects what has been documented at the lesion site. The participants included 22 CL patients diagnosed with a positive PCR. PBMCs were stimulated for 72 h with a soluble leishmania antigen (SLA). Biopsies obtained from the edge of the ulcers were incubated for the same period. Cytokines in supernatants were assessed via ELISA. TNF, IL-1β, IL-6, IL-17, and granzyme B (GzmB) were higher in the supernatants of biopsies than in PBMCs, but IFN-γ was higher in the supernatants of PBMCs than in biopsies. There was a positive correlation between IFN-γ and TNF in PBMCs, and an inverse correlation between TNF and IL-10 in the cells from the lesion site. A strong correlation between IL-1β, IL-17, and GzmB was observed in the biopsies, and a positive correlation was detected between these cytokines and the lesion size. Our results indicate that the immune response in L. braziliensis lesions is different from that observed in peripheral blood, and our data suggest that in addition to IL-1β and GzmB, IL-17 participates in the pathology of CL.
]]>Pathogens doi: 10.3390/pathogens13030198
Authors: Mathy Matungala-Pafubel Junior Bulabula-Penge Meris Matondo-Kuamfumu Samy Esala François Edidi-Atani Elisabeth Pukuta-Simbu Paul Tshiminyi-Munkamba Yannick Tutu Tshia N’kasar Trésor Katanga Etienne Ndomba-Mukanya Delphine Mbonga-Mande Lionel Baketana-Kinzonzi Eddy Kinganda-Lusamaki Daniel Mukadi-Bamuleka Fabrice Mambu-Mbika Placide Mbala-Kingebeni Edith Nkwembe-Ngabana Antoine Nkuba-Ndaye Daniel Okitundu-Luwa Steve Ahuka-Mundeke
Polio-associated paralysis is one of the diseases under national surveillance in the Democratic Republic of the Congo (DRC). Although it has become relatively rare due to control measures, non-polio paralysis cases are still reported and constitute a real problem, especially for etiological diagnosis, which is necessary for better management and response. From September 2022 to April 2023, we investigated acute flaccid paralysis (AFP) cases in Kinshasa following an alert from the Provincial Division of Health. All suspected cases and their close contacts were investigated and sampled. Among the 57 sampled patients, 21 (36.8%) were suspects, and 36 (63.2%) were contacts. We performed several etiological tests available in the laboratory, targeting viruses, including Poliovirus, Influenza virus, SARS-CoV-2, Enterovirus, and arboviruses. No virus material was detected, but the serological test (ELISA) detected antibodies against Chikungunya Virus, i.e., 47.4% (27/57) for IgM and 22.8% (13/57) for IgG. Among suspected cases, we detected 33.3% (7/21) with anti-Chikungunya IgM and 14.3% (3/21) of anti-Chikungunya IgG. These results highlight the importance of enhancing the epidemiological surveillance of Chikungunya.
]]>Pathogens doi: 10.3390/pathogens13030197
Authors: Kira M. Zack Trent Sorenson Suresh G. Joshi
Bacteria express a plethora of efflux pumps that can transport structurally varied molecules, including antimicrobial agents and antibiotics, out of cells. Thus, efflux pump systems participate in lowering intracellular concentrations of antibiotics, which allows phenotypic multidrug-resistant (MDR) bacteria to survive effectively amid higher concentrations of antibiotics. Acinetobacter baumannii is one of the classic examples of pathogens that can carry multiple efflux pump systems, which allows these bacteria to be MDR-to-pan-drug resistant and is now considered a public health threat. Therefore, efflux pumps in A. baumannii have gained major attention worldwide, and there has been increased interest in studying their mechanism of action, substrates, and potential efflux pump inhibitors (EPIs). Efflux pump inhibitors are molecules that can inhibit efflux pumps, rendering pathogens susceptible to antimicrobial agents, and are thus considered potential therapeutic agents for use in conjunction with antibiotics. This review focuses on the types of various efflux pumps detected in A. baumannii, their molecular mechanisms of action, the substrates they transport, and the challenges in developing EPIs that can be clinically useful in reference to A. baumannii.
]]>Pathogens doi: 10.3390/pathogens13030196
Authors: Sarah N. Wieser Susana M. Giuliano Juan Reategui Ordoñez Ximena Barriga Marcapura Luis V. M. Olivera Miguel Angel Chavez Chavez Fumagalli Leonhard Schnittger Mónica Florin-Christensen
Sarcocystis spp. are coccidian protozoans belonging to the Apicomplexa phylum. As with other members of this phylum, they are obligate intracellular parasites with complex cellular machinery for the invasion of host cells. Sarcocystis spp. display dixenous life cycles, involving a predator and a prey as definitive and intermediate hosts, respectively. Specifically, these parasites develop sarcocysts in the tissues of their intermediate hosts, ranging in size from microscopic to visible to the naked eye, depending on the species. When definitive hosts consume sarcocysts, infective forms are produced in the digestive system and discharged into the environment via feces. Consumption of oocyst-contaminated water and pasture by the intermediate host completes the parasitic cycle. More than 200 Sarcocystis spp. have been described to infect wildlife, domestic animals, and humans, some of which are of economic or public health importance. Interestingly, Old World camelids (dromedary, domestic Bactrian camel, and wild Bactrian camel) and New World or South American camelids (llama, alpaca, guanaco, and vicuña) can each be infected by two different Sarcocystis spp: Old World camelids by S. cameli (producing micro- and macroscopic cysts) and S. ippeni (microscopic cysts); and South American camelids by S. aucheniae (macroscopic cysts) and S. masoni (microscopic cysts). Large numbers of Old and New World camelids are bred for meat production, but the finding of macroscopic sarcocysts in carcasses significantly hampers meat commercialization. This review tries to compile the information that is currently accessible regarding the biology, epidemiology, phylogeny, and diagnosis of Sarcocystis spp. that infect Old and New World camelids. In addition, knowledge gaps will be identified to encourage research that will lead to the control of these parasites.
]]>Pathogens doi: 10.3390/pathogens13030195
Authors: Argul Issilbayeva Aiym Kaiyrlykyzy Elizaveta Vinogradova Zharkyn Jarmukhanov Samat Kozhakhmetov Aliya Kassenova Madiyar Nurgaziyev Nurislam Mukhanbetzhanov Dinara Alzhanova Gulnaz Zholdasbekova Sholpan Askarova Almagul R. Kushugulova
Recent studies have suggested that periodontal disease and alterations in the oral microbiome may be associated with cognitive decline and Alzheimer’s disease (AD) development. Here, we report a case-control study of oral microbiota diversity in AD patients compared to healthy seniors from Central Asia. We have characterized the bacterial taxonomic composition of the oral microbiome from AD patients (n = 64) compared to the healthy group (n = 71) using 16S ribosomal RNA sequencing. According to our results, the oral microbiome of AD has a higher microbial diversity, with an increase in Firmicutes and a decrease in Bacteroidetes in the AD group. LEfSe analysis showed specific differences at the genus level in both study groups. A region-based analysis of the oral microbiome compartment in AD was also performed, and specific differences were identified, along with the absence of differences in bacterial richness and on the functional side. Noteworthy findings demonstrated the decrease in periodontitis-associated bacteria in the AD group. Distinct differences were revealed in the distribution of metabolic pathways between the two study groups. Our study confirms that the oral microbiome is altered in AD. However, a comprehensive picture of the complete composition of the oral microbiome in patients with AD requires further investigation.
]]>Pathogens doi: 10.3390/pathogens13030194
Authors: Prabhat K. Talukdar Maryam Alnoman Mahfuzur R. Sarker
In this study, we investigated the spore germination phenotype of Clostridium perfringens strains isolated from diarrheic animals (animal strains). The transcripts of germination-specific genes and their protein products were also measured. Our study found the following results: (i) animal strains spores germinated at a slower rate with AK (mixture of L-asparagine and KCl), L-cysteine, or L-lysine, but the extent of germination varied based on strains and germinants used; (ii) none of the amino acids (excluding L-cysteine and L-lysine) were identified as a universal germinant for spores of animal strains; (iii) animal strain spores germinated better at a pH range of 6.0–7.0; (iv) all tested germination-specific genes were expressed in animal strains; the levels of expression of major germinant receptor gene (gerKC) were higher and the cortex hydrolysis machinery genes (cspB and sleC) were lower in animal strains, compared to the food poisoning strain SM101; and (v) the levels of CspB and SleC were significantly lower in spores of animal strains compared to strain SM101, suggesting that these animal strains lack an efficient spore cortex hydrolysis machinery. In summary, our findings suggest that the poor or slow spore germination in C. perfringens animal strains might be due to incomplete spore cortex hydrolysis.
]]>Pathogens doi: 10.3390/pathogens13030193
Authors: Florian Sänger Michèle Bergmann Katrin Hartmann René Dörfelt
A three-year-old, intact female mix-breed dog, weighing 30 kg, was presented due to vomitus and diarrhea. At presentation, the patient had a slightly reduced general condition and moderately enlarged mandibular and popliteal lymph nodes. The initial blood work showed severe azotemia and hypoalbuminemia. In the urinalysis, marked proteinuria with a urine protein/creatinine ratio (UPC) of 4.69 was found. Further workup showed a high leishmania antibody titer. The dog was diagnosed with leishmaniosis and glomerulonephritis. Initial treatment consisted of intravenous fluid therapy, allopurinol, miltefosine, amlodipine, clopidogrel, and a diet with a low purine content. Creatinine temporarily decreased but increased again after three days. For further supportive treatment, intermittent hemodialysis in combination with hemoperfusion with the cytosorb® adsorber was performed. A total blood volume of 17.7 L was processed within three hours. Thereafter, immunoadsorption (IA) was performed with the COM.TEC® and ADAsorb® platforms and a LIGASORB® adsorber to eliminate circulating immunocomplexes. Treatment time for IA was two hours with a blood flow of 50 mL/min. A total plasma volume of 2.4 L was processed. Over the following days, creatinine declined, and the patient improved significantly. UPC decreased to 1.74 on day 17 after IA. The patient was discharged after two and a half weeks. Two years after the initial event, the patient is still in excellent condition, with creatinine, UPC, and albumin levels in the reference range. Therefore, IA might be an additional therapeutic option for dogs with leishmaniosis-induced glomerulonephritis and subsequent severe azotemia to improve immunocomplex-mediated glomerulonephritis.
]]>Pathogens doi: 10.3390/pathogens13030192
Authors: Maria Soltero-Rivera Claire Shaw Boaz Arzi Milinda Lommer Bart Weimer
Feline chronic gingivostomatitis (FCGS) is a debilitating inflammatory oral mucosal disease with a multifactorial etiology. The clinical diagnosis of FCGS is made based on inspection of severe inflammatory lesions and histological confirmation rather than a molecular diagnostic outcome. This gap limits the ability to provide an early diagnosis. In this report, we seek to provide additional diagnostic tools using genomics to aid in providing clinically relevant information. The use of in-depth diagnostic tools, like transcriptomics of diseased tissues, to diagnose FCGS and stratify patients into predictive treatment response groups would dramatically improve both clinical decisions and patient outcomes. In this study, we addressed the gap in diagnostic options using transcriptomic analysis of caudal oral mucosal swab specimens coupled to detailed medical record linkage of FCGS-affected cats undergoing tooth extractions and in some cases administration of mesenchymal stromal cells (MSCs). To better identify markers of disease and potential response to treatment, the transcriptomes of FCGS-afflicted cats were compared to those of healthy cats and those with chronic periodontitis to clearly establish diagnostic biomarker signal transduction connections. Phosphatidylinositol 3-kinase/Ak strain transforming (PI3K/AKT) and stress-activated protein kinases/Jun N-terminal kinase (SAP/JNK) signaling pathways were significantly differentially regulated in FCGS-afflicted cats. Activation of these pathways also differed in the treatment response groups. In conjunction, the enzymes Caspase 4 (CASP4), matrix metalloproteinase-8 (MMP8), and prostaglandin-endoperoxide synthase 2 (PTGS2) were identified as potential biomarkers for the prediction of treatment response outcomes. The observations in the case study support the use of transcriptomics of FCGS patients to contribute to improved molecular diagnostics for the diagnosis and treatment of FCGS.
]]>Pathogens doi: 10.3390/pathogens13030191
Authors: Luis Martinez-Sobrido Marta L. DeDiego
A previously unknown coronavirus, named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), emerged in the city of Wuhan, China, in December 2019 [...]
]]>Pathogens doi: 10.3390/pathogens13030190
Authors: Jennifer L. Adema Aileen Ahiskali Madiha Fida Krutika Mediwala Hornback Ryan W. Stevens Christina G. Rivera
There was an error in the original publication [...]
]]>Pathogens doi: 10.3390/pathogens13030189
Authors: Valentina Siciliano Flavio Sangiorgi Pierluigi Del Vecchio Layla Vahedi Maya Manuela Gross Angela Saviano Veronica Ojetti
Long-acting lipoglycopeptides (LGPs), such as dalbavancin and oritavancin, are semisynthetic antibiotics known for their strong effectiveness against a wide array of Gram-positive bacteria. This includes Staphylococcus aureus, both methicillin-sensitive (MSSA) and methicillin-resistant (MRSA) strains, coagulase-negative Staphylococci (CoNS), streptococci, and vancomycin-sensitive Enterococcus faecalis. A literature search was conducted on PubMed and on ClinicalTrials.gov to identify articles published until July 2023 investigating the use of oritavancin and dalbavancin in clinical practice. The review included case reports, case series, observational studies, and clinical studies. Although more consistent data are needed, LGPs seem to be a good alternative that may provide a quicker hospital discharge and reduce long-term intravenous access and therapy. This is attributed to their unique pharmacologic and pharmacokinetic characteristics. More quality data (i.e., number of patients treated with clinical success) are needed before clinicians may use these therapies more widely.
]]>Pathogens doi: 10.3390/pathogens13030188
Authors: Boyoon Choi Hien Thi Vu Hai Thi Vu Magdalena Radwanska Stefan Magez
Trypanosomes are single-celled extracellular parasites that infect mammals, including humans and livestock, causing global public health concerns and economic losses. These parasites cycle between insect vectors, such as tsetse flies and vertebrate hosts, undergoing morphological, cellular, and biochemical changes. They have remarkable immune evasion mechanisms to escape the host’s innate and adaptive immune responses, such as surface coat antigenic variation and the induction of the loss of specificity and memory of antibody responses, enabling the prolongation of infection. Since trypanosomes circulate through the host body in blood and lymph fluid and invade various organs, understanding the interaction between trypanosomes and tissue niches is essential. Here, we present an up-to-date overview of host–parasite interactions and survival strategies for trypanosomes by introducing and discussing the latest studies investigating the transcriptomics of parasites according to life cycle stages, as well as host cells in various tissues and organs, using single-cell and spatial sequencing applications. In recent years, this information has improved our understanding of trypanosomosis by deciphering the diverse populations of parasites in the developmental process, as well as the highly heterogeneous immune and tissue-resident cells involved in anti-trypanosome responses. Ultimately, the goal of these approaches is to gain an in-depth understanding of parasite biology and host immunity, potentially leading to new vaccination and therapeutic strategies against trypanosomosis.
]]>Pathogens doi: 10.3390/pathogens13030187
Authors: Nika Lovšin Bhavani Gangupam Martina Bergant Marušič
APOBEC3 proteins are cytidine deaminases that play a crucial role in the innate immune response against viruses, including DNA viruses. Their main mechanism for restricting viral replication is the deamination of cytosine to uracil in viral DNA during replication. This process leads to hypermutation of the viral genome, resulting in loss of viral fitness and, in many cases, inactivation of the virus. APOBEC3 proteins inhibit the replication of a number of DNA tumour viruses, including herpesviruses, papillomaviruses and hepadnaviruses. Different APOBEC3s restrict the replication of different virus families in different ways and this restriction is not limited to one APOBEC3. Infection with DNA viruses often leads to the development and progression of cancer. APOBEC3 mutational signatures have been detected in various cancers, indicating the importance of APOBEC3s in carcinogenesis. Inhibition of DNA viruses by APOBEC3 proteins appears to play a dual role in this process. On the one hand, it is an essential component of the innate immune response to viral infections, and, on the other hand, it contributes to the pathogenesis of persistent viral infections and the progression of cancer. The current review examines the complex interplay between APOBEC3 proteins and DNA viruses and sheds light on the mechanisms of action, viral countermeasures and the impact on carcinogenesis. Deciphering the current issues in the interaction of APOBEC/DNA viruses should enable the development of new targeted cancer therapies.
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