Pathogens

14 pages, 967 KiB

Open AccessArticle

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

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

Pathogens 2024, 13(5), 382; https://doi.org/10.3390/pathogens13050382 - 03 May 2024

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Abstract

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

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

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

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9 pages, 385 KiB

Open AccessArticle

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

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

Pathogens 2024, 13(5), 381; https://doi.org/10.3390/pathogens13050381 - 02 May 2024

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Abstract

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

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

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

12 pages, 3806 KiB

Open AccessArticle

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

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

Pathogens 2024, 13(5), 380; https://doi.org/10.3390/pathogens13050380 - 02 May 2024

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Abstract

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

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

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

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13 pages, 976 KiB

Open AccessArticle

The Tomato Variety Affects the Survival of Shigella flexneri 2a in Fruit Pericarp

by Tania Henriquez, Simona Guerra, Marta Nerini, Diane Purchase and Massimiliano Marvasi

Pathogens 2024, 13(5), 379; https://doi.org/10.3390/pathogens13050379 - 01 May 2024

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Abstract

The presence of enteric pathogens in produce can serve as a significant means of transmitting infections to consumers. Notably, tomatoes, as a type of produce, have been implicated in outbreaks caused by various human pathogens, such as Salmonella enterica and pathogenic Escherichia coli. [...] Read more.

The presence of enteric pathogens in produce can serve as a significant means of transmitting infections to consumers. Notably, tomatoes, as a type of produce, have been implicated in outbreaks caused by various human pathogens, such as Salmonella enterica and pathogenic Escherichia coli. However, the survival characteristics of Shigella spp. in tomatoes have not been thoroughly investigated. In this study, we assess the survival of S. flexneri 2a in two distinct varieties of post-harvested tomatoes. S. flexneri 2a was used to inoculate both regular-sized Vine tomatoes and cherry-type Mini Plum tomatoes. Our findings reveal no significant difference in Shigella survival in the pericarp of both varieties on day 2 post-inoculation. However, a significant disparity emerges on day 6, where all recovered Shigella colonies exclusively belong to the Mini Plum variety, with none associated with the Vine type. When Shigella was inoculated into the locular cavity (deep inoculation), no significant difference between varieties was observed. Additionally, we investigate the potential role of the SRL pathogenicity island (SRL PAI) in the survival and fitness of S. flexneri 2a in post-harvested tomatoes. Our results indicate that while the SRL PAI is not linked to the survival of the strains in tomato, it does impact their fitness. These findings underscore the variability in Shigella strains’ survival capabilities depending on the tomato variety, highlighting the importance of understanding Shigella ecology beyond the human host and identifying molecular determinants influencing bacterial survival to mitigate the risk of future outbreaks. The significance of this data on Shigella persistence in fresh vegetables should not be underestimated, as even a small number of Shigella cells can pose a threat to the health of individuals. Full article

(This article belongs to the Section Bacterial Pathogens)

17 pages, 2656 KiB

Open AccessSystematic Review

Helminth Prevalence in European Deer with a Focus on Abomasal Nematodes and the Influence of Livestock Pasture Contact: A Meta-Analysis

by Tony L. Brown and Eric R. Morgan

Pathogens 2024, 13(5), 378; https://doi.org/10.3390/pathogens13050378 - 01 May 2024

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Abstract

Deer are susceptible to infection with parasitic helminths, including species which are of increasing economic concern to the livestock industry due to anthelmintic drug resistance. This paper systematically collates helminth prevalence data from deer across Europe and explores patterns in relation to host [...] Read more.

Deer are susceptible to infection with parasitic helminths, including species which are of increasing economic concern to the livestock industry due to anthelmintic drug resistance. This paper systematically collates helminth prevalence data from deer across Europe and explores patterns in relation to host and parasite species, as well as landscape factors. A livestock pasture contact index (LPCI) is developed to predict epidemiological overlap between deer and livestock, and hence to examine deer helminth fauna in the context of their surrounding environment. Fifty-eight studies comprising fallow (Dama dama), red (Cervus elaphus), roe (Capreolus capreolus) and sika (Cervus nippon) deer were identified. Deer populations in “likely” contact with livestock pasture had a higher mean prevalence of the abomasal nematodes Haemonchus contortus, Ostertagia ostertagi, Teladorsagia circumcincta and Trichostrongylus axei (p = 0.01), which are common in livestock and not primarily associated with deer. Roe deer populations had a higher prevalence of T. circumcincta (p = 0.02) and T. axei (p = 0.01) than fallow deer and a higher prevalence of H. contortus than both red (p = 0.01) and fallow deer (p = 0.02). Liver fluke and lungworm species were present sporadically at low prevalence, while the abomasal nematode Ashworthius sidemi occurred locally at high prevalence. Insights from this research suggest that deer helminth fauna is reflective of their surrounding environment, including the livestock species which inhabit areas of shared grazing. This is explored from an epidemiological perspective, and the prospect of helminth transmission between wild and domestic hosts is discussed, including drug-resistant strains, alongside the role of helminths as indicators relevant to the transmission of other pathogens at the wildlife–livestock interface. Full article

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

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6 pages, 481 KiB

Open AccessProject Report

Polio Surge Capacity Support Program Contributions to Building Country Capacities in Support of Polio Outbreak Preparedness and Response: Lessons Learned and Remaining Challenges

by Fikru Abebe, Victor Anochieboh Eboh, Mesfin Belew Weldetsadik, Ibrahima Kone, Tessema Assegid Kebede, Paul Thomas Harries and Veh Kesse Fabien Diomande

Pathogens 2024, 13(5), 377; https://doi.org/10.3390/pathogens13050377 - 01 May 2024

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Abstract

Despite coordinated efforts at global level, through the Global Polio Eradication Initiative (GPEI), poliomyelitis disease (Polio) is still a major public health issue. The wild poliovirus type-1 (WPV1) is still endemic in Afghanistan and Pakistan, and new circulations of the WPV1 were confirmed [...] Read more.

Despite coordinated efforts at global level, through the Global Polio Eradication Initiative (GPEI), poliomyelitis disease (Polio) is still a major public health issue. The wild poliovirus type-1 (WPV1) is still endemic in Afghanistan and Pakistan, and new circulations of the WPV1 were confirmed in southeast Africa in 2021, in Malawi and Mozambique. The circulating vaccine derived polioviruses (cVDPV) are also causing outbreaks worldwide. The Task Force for Global Health (TFGH)’s Polio Surge Capacity Support Program, established in 2019, is an effort to reinforce the existing partnership with the GPEI to strengthen countries’ capacities for polio outbreak preparedness and response. In four years, its coordinated efforts with GPEI partners have resulted in a remarkable improvement in the early detection of poliovirus circulation and reducing the missed children gaps in many countries. However, these encouraging results cannot hide an increasingly complex programmatic environment with numerous funding and operational challenges. Full article

(This article belongs to the Special Issue Human Poliovirus)

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23 pages, 5917 KiB

Open AccessArticle

Involvement of Inflammatory Cytokines, Renal NaPi-IIa Cotransporter, and TRAIL Induced-Apoptosis in Experimental Malaria-Associated Acute Kidney Injury

by Gustavo Martins Simião, Kleber Simônio Parreira, Sandra Gabriela Klein, Flávia Batista Ferreira, Fernanda de Souza Freitas, Eduardo Ferreira da Silva, Neide Maria Silva, Murilo Vieira da Silva and Wânia Rezende Lima

Pathogens 2024, 13(5), 376; https://doi.org/10.3390/pathogens13050376 - 01 May 2024

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Abstract

The murine model of experimental cerebral malaria (ECM) induced by Plasmodium berghei ANKA was used to investigate the relationship among pro-inflammatory cytokines, alterations in renal function biomarkers, and the induction of the TRAIL apoptosis pathway during malaria-associated acute kidney injury (AKI). Renal function [...] Read more.

The murine model of experimental cerebral malaria (ECM) induced by Plasmodium berghei ANKA was used to investigate the relationship among pro-inflammatory cytokines, alterations in renal function biomarkers, and the induction of the TRAIL apoptosis pathway during malaria-associated acute kidney injury (AKI). Renal function was evaluated through the measurement of plasma creatinine and blood urea nitrogen (BUN). The mRNA expression of several cytokines and NaPi-IIa was quantified. Kidney sections were examined and cytokine levels were assessed using cytometric bead array (CBA) assays. The presence of glomerular IgG deposits and apoptosis-related proteins were investigated using in situ immunofluorescence assays and quantitative real-time PCR, respectively. NaPi-IIa downregulation in the kidneys provided novel insights into the pathogenesis of hypophosphatemia during CM. Histopathological analysis revealed characteristic features of severe malaria-associated nephritis, including glomerular collapse and tubular alterations. Pro-inflammatory cytokines, such as TNF-α, IL-1β, and IL-6, were upregulated. The TRAIL apoptosis pathway was significantly activated, implicating its role in renal apoptosis. The observed alterations in renal biomarkers and the downregulation of NaPi-IIa shed light on potential mechanisms contributing to renal dysfunction in ECM. The intricate balance between pro- and anti-inflammatory cytokines, along with the activation of the TRAIL apoptosis pathway, highlights the complexity of malaria-associated AKI and provides new therapeutic targets. Full article

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9 pages, 397 KiB

Open AccessArticle

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

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

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

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Abstract

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

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

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

15 pages, 1100 KiB

Open AccessArticle

A Conservative Mutant Version of the Mrr1 Transcription Factor Correlates with Reduced Sensitivity to Fludioxonil in Botrytis cinerea

by Charleen Copier, Claudio Osorio-Navarro, Jonathan E. Maldonado, Jaime Auger, Herman Silva and Marcela Esterio

Pathogens 2024, 13(5), 374; https://doi.org/10.3390/pathogens13050374 - 30 Apr 2024

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Abstract

Fludioxonil is a highly effective phenylpyrrole fungicide for controlling Botrytis cinerea. Although the field efficacy of fludioxonil remains high, Botrytis cinerea isolates with reduced sensitivity have been reported globally. The molecular target of fludioxonil still remains unknown; however, a mechanism of reduced [...] Read more.

Fludioxonil is a highly effective phenylpyrrole fungicide for controlling Botrytis cinerea. Although the field efficacy of fludioxonil remains high, Botrytis cinerea isolates with reduced sensitivity have been reported globally. The molecular target of fludioxonil still remains unknown; however, a mechanism of reduced sensitivity to fludioxonil underlies the overexpression of the ATP binding cassette (ABC) transporter AtrB in a dependent pathway of the Mrr1 transcription factor. Fludioxonil is a key player in controlling B. cinerea infection in table grapes in Chile. However, some isolates with a reduced sensitivity to fludioxonil were recently detected. This study observed endogenous atrB overexpression in Chilean isolates with reduced sensitivity to fludioxonil (n = 22) compared to the sensitive isolates (n = 10). All isolates increased the expression of atrB in a growth medium supplemented with fludioxonil (0.05 μg/mL). However, sensitive isolates showed lower atrB expression than those with reduced fludioxonil sensitivity. Remarkably, a mutant version of the transcription factor Mrr1 carrying 21 amino acid modifications was identified in all isolates with reduced sensitivity to fludioxonil. These changes alter the protein’s transcription factor domain and the C-terminal portion of the protein but not the Zn (2)-C6 fungal-type DNA-binding domain. These results suggest a direct relationship between the conserved and divergent mutant version of mrr1 and sensitivity to fludioxonil. This study provides a new target for developing molecular diagnostic strategies to monitor B. cinerea’s sensitivity to fludioxonil in the field. Full article

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14 pages, 3703 KiB

Open AccessFeature PaperArticle

Effect of Stevioside (Stevia rebaudiana) on Entamoeba histolytica Trophozoites

by Karla Jocelyn Ortega-Carballo, Karla Montserrat Gil-Becerril, Karla Berenice Acosta-Virgen, Sael Casas-Grajales, Pablo Muriel and Víctor Tsutsumi

Pathogens 2024, 13(5), 373; https://doi.org/10.3390/pathogens13050373 - 30 Apr 2024

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Abstract

Human amoebiasis still represents a major health problem worldwide. Metronidazole has been used as the most common drug to treat the disease; however, it is also known that the drug causes undesirable side effects. This has led to the search for new pharmacological [...] Read more.

Human amoebiasis still represents a major health problem worldwide. Metronidazole has been used as the most common drug to treat the disease; however, it is also known that the drug causes undesirable side effects. This has led to the search for new pharmacological alternatives which include phytochemical compounds with antiamoebic effects. We analyzed the amoebicidal activity of stevioside (STV), a diterpene glycoside present in Stevia rebaudiana, on trophozoites of E. histolytica. Different concentrations of STV were tested, and an inhibitory concentration of 50% of cell viability (IC₅₀) was determined with an exposition of 9.53 mM for 24 h. Trophozoites exposed to STV showed morphological changes evidenced by the decrease in the basic structures related to the movement and adherence to the substrate, as well as ultrastructural features characterized by a loss of regularity on the cell membrane, an increase in cytoplasmic granularity, and an increase in apparent autophagic vacuoles. Also, the decrease in cysteine protease expression and the proteolytic activity of trophozoites to degrade the cell monolayer were analyzed. A histological analysis of hamster livers inoculated with trophozoites and treated with STV showed changes related to the granulomatous reaction of the liver parenchymal tissue. Our results constitute the first report related to the possible use of STV as a therapeutic alternative in amoebiasis. Full article

(This article belongs to the Special Issue Prevalence, Pathology, and Alternative Control of Intestinal Parasites)

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22 pages, 8658 KiB

Open AccessArticle

Insights into Wheat Genotype‒Sphaerodes mycoparasitica Interaction to Improve Crop Yield and Defence against Fusarium graminearum: An Integration of FHB Biocontrol in Canadian Wheat Breeding Programmes

by Antonia Powell, Seon Hwa Kim, Pierre Hucl and Vladimir Vujanovic

Pathogens 2024, 13(5), 372; https://doi.org/10.3390/pathogens13050372 - 30 Apr 2024

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Abstract

Fusarium head blight (FHB) is a major threat to wheat crop production and food security worldwide. The creation of resistant wheat cultivars is an essential component of an integrated strategy against Fusarium graminearum, the primary aetiological agent that causes FHB. The results [...] Read more.

Fusarium head blight (FHB) is a major threat to wheat crop production and food security worldwide. The creation of resistant wheat cultivars is an essential component of an integrated strategy against Fusarium graminearum, the primary aetiological agent that causes FHB. The results of this study show that the deployment of proto-cooperative interactions between wheat genotypes and mycoparasitic biocontrol agents (BCAs) can improve crop yield and plant resistance in controlling the devastating effects of FHB on wheat agronomic traits. A Fusarium-specific mycoparasite, Sphaerodes mycoparasitica, was found to be compatible with common and durum wheat hosts, thus allowing the efficient control of F. graminearum infection in plants. Four genotypes of wheat, two common wheat, and two durum wheat cultivars with varying FHB resistance levels were used in this greenhouse study. The BCA treatments decreased FHB symptoms in all four cultivars and improved the agronomic traits such as spike number, spike weight, seed weight, plant biomass, and plant height which are vital to grain yield. Conversely, the F. graminearum 3ADON chemotype treatment decreased the agronomic trait values by up to 44% across cultivars. Spike number, spike weight, and seed weight were the most improved traits by the BCA. A more measurable improvement in agronomic traits was observed in durum wheat cultivars compared to common wheat. Full article

(This article belongs to the Special Issue Current Research on Fusarium: 2nd Edition)

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19 pages, 5365 KiB

Open AccessArticle

Anatomical Vascular Differences and Leishmania-Induced Vascular Morphological Changes Are Associated with a High Parasite Load in the Skin of Dogs Infected with Leishmania infantum

by Francini N. Ribeiro, Tainã L. de Souza, Rodrigo C. Menezes, Lucas Keidel, João Paulo R. dos Santos, Igor J. da Silva, Marcelo Pelajo-Machado, Fernanda N. Morgado and Renato Porrozzi

Pathogens 2024, 13(5), 371; https://doi.org/10.3390/pathogens13050371 - 30 Apr 2024

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Abstract

Canine visceral leishmaniasis (CVL), caused by the protozoan Leishmania infantum, affects several organs, including the skin. Dogs are considered the major domestic reservoir animals for leishmaniasis, and through their highly parasitized skin, they can serve as a source of infection for sandfly [...] Read more.

Canine visceral leishmaniasis (CVL), caused by the protozoan Leishmania infantum, affects several organs, including the skin. Dogs are considered the major domestic reservoir animals for leishmaniasis, and through their highly parasitized skin, they can serve as a source of infection for sandfly vectors. Therefore, studies of the skin parasite–host relationship can contribute to the understanding of the infectious dissemination processes of parasites in the dermis and help to identify targets for diagnosis and treatment. Thus, the aim of this study was to evaluate the association of anatomical vascular differences and Leishmania-induced vascular morphological changes with clinical signs and parasite load by analyzing the ear and abdominal skin from dogs naturally infected with L. infantum. Paired samples of ear and abdominal skin from L. infantum-positive dogs (n = 26) were submitted for histological and immunohistochemistry analyses. The ear skin samples showed a more intense and more diffusely distributed granulomatous inflammatory reaction, a higher number and larger diameter of blood vessels, increased parasite load, higher expression of VEGF+ (vascular endothelial growth factor) and MAC 387+ (calprotectin) recently infiltrating cells, and more intense collagen disruption compared to the abdominal skin samples. Intracellular amastigotes were observed in blood vessels and inside endothelial cells and were diffusely distributed throughout the dermis in the ear skin samples. The NOS2/MAC387+ cell ratio was lower in the ear skin samples than in those of the abdomen, suggesting that in the ear dermis, the inflammatory infiltrate was less capable of producing NO and thereby control the parasite load. Together, these findings indicate how parasites and immune cells are distributed in the skin and suggest an important role for dermal vascularization in cellular influx and thereby in parasite dissemination through the skin of naturally infected dogs. Full article

(This article belongs to the Special Issue Canine Leishmaniasis: Epidemiology, Diagnosis, Pathogenesis, Treatment and Vaccine)

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11 pages, 238 KiB

Open AccessReview

Is Pollution the Primary Driver of Infectious Syndemics?

by Merrill Singer

Pathogens 2024, 13(5), 370; https://doi.org/10.3390/pathogens13050370 - 30 Apr 2024

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Abstract

Syndemics, the adverse interaction of two or more coterminous diseases or other negative health conditions, have probably existed since human settlement, plant and animal domestication, urbanization, and the growth of social inequality beginning about 10–12,000 years ago. These dramatic changes in human social [...] Read more.

Syndemics, the adverse interaction of two or more coterminous diseases or other negative health conditions, have probably existed since human settlement, plant and animal domestication, urbanization, and the growth of social inequality beginning about 10–12,000 years ago. These dramatic changes in human social evolution significantly increased opportunities for the spread of zoonotic infectious diseases in denser human communities with increased sanitation challenges. In light of a growing body of research that indicates that anthropogenic air pollution causes numerous threats to health and is taking a far greater toll on human life and wellbeing than had been reported, this paper proposes the possibility that air pollution is now the primary driver of infectious disease syndemics. In support of this assertion, this paper reviews the growth and health impacts of air pollution, the relationship of air pollution to the development and spread of infectious diseases, and reported cases of air pollution-driven infectious disease syndemics, and presents public health recommendations for leveraging the biosocial insight of syndemic theory in responding to infectious disease. Full article

11 pages, 537 KiB

Open AccessArticle

Stenotrophomonas maltophilia Outbreak in an ICU: Investigation of Possible Routes of Transmission and Implementation of Infection Control Measures

by Maria Luisa Cristina, Marina Sartini, Gianluca Ottria, Elisa Schinca, Giulia Adriano, Leonello Innocenti, Marco Lattuada, Stefania Tigano, David Usiglio and Filippo Del Puente

Pathogens 2024, 13(5), 369; https://doi.org/10.3390/pathogens13050369 - 29 Apr 2024

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Abstract

Stenotrophomonas maltophilia, a non-fermentative, ubiquitous, gram-negative aerobic bacterium, is associated with high mortality rates, particularly in immunocompromised or debilitated patients. The prevalence rate of ICU-acquired pneumonia episodes caused by this microorganism has been found to be 2%. S. maltophilia has been identified [...] Read more.

Stenotrophomonas maltophilia, a non-fermentative, ubiquitous, gram-negative aerobic bacterium, is associated with high mortality rates, particularly in immunocompromised or debilitated patients. The prevalence rate of ICU-acquired pneumonia episodes caused by this microorganism has been found to be 2%. S. maltophilia has been identified as one of the top 10 microorganisms responsible for such infections in EU/EEA countries. This study describes an outbreak of S. maltophilia in an intensive care unit of a hospital in northern Italy. This includes an epidemiological investigation of the cases, the environmental microbiological controls carried out, a comparison of the strains by multilocus sequence typing (MLST), and the measures taken to prevent and control the outbreak. Among the seven clinical isolates of S. maltophilia analyzed herein, six demonstrated susceptibilities to trimethoprim–sulfamethoxazole. Conversely, one isolate of S. maltophilia exhibited resistance to first-line antibiotics. ST was found to be identical for six patients (ST 4), as well as in the environmental feedback on the trolley of ^{Box 2}. The analysis of the temporal and spatial progression of the outbreak has suggested that the transmission of S. maltophilia may have occurred through cross-transmission during care practices. Full article

(This article belongs to the Special Issue Hospital-Acquired Infections and Multidrug-Resistant (MDR) Pathogens)

11 pages, 434 KiB

Open AccessArticle

Presence and Immunoreactivity of Aggregatibacter actinomycetemcomitans in Rheumatoid Arthritis

by Anna Svärd, Riccardo LoMartire, Klara Martinsson, Carina Öhman, Alf Kastbom and Anders Johansson

Pathogens 2024, 13(5), 368; https://doi.org/10.3390/pathogens13050368 - 29 Apr 2024

Viewed by 276

Abstract

The presence of periodontal pathogens is associated with an increased prevalence of rheumatoid arthritis (RA). The systemic antibody response to epitopes of these bacteria is often used as a proxy to study correlations between bacteria and RA. The primary aim of the present [...] Read more.

The presence of periodontal pathogens is associated with an increased prevalence of rheumatoid arthritis (RA). The systemic antibody response to epitopes of these bacteria is often used as a proxy to study correlations between bacteria and RA. The primary aim of the present study is to examine the correlation between the presence of Aggregatibacter actinomycetemcomitans (Aa) in the oral cavity and serum antibodies against the leukotoxin (LtxA) produced by this bacterium. The salivary presence of Aa was analyzed with quantitative PCR and serum LtxA ab in a cell culture-based neutralization assay. The analyses were performed on samples from a well-characterized RA cohort (n = 189) and a reference population of blood donors (n = 101). Salivary Aa was present in 15% of the RA patients and 6% of the blood donors. LtxA ab were detected in 19% of RA-sera and in 16% of sera from blood donors. The correlation between salivary Aa and serum LtxA ab was surprisingly low (rho = 0.55 [95% CI: 0.40, 0.68]). The presence of salivary Aa showed no significant association with any of the RA-associated parameters documented in the cohort. A limitation of the present study is the relatively low number of individuals with detectable concentrations of Aa in saliva. Moreover, in the comparison of detectable Aa prevalence between RA patients and blood donors, we assumed that the two groups were equivalent in other Aa prognostic factors. These limitations must be taken into consideration when the result from the study is interpreted. We conclude that a systemic immune response to Aa LtxA does not fully reflect the prevalence of Aa in saliva. In addition, the association between RA-associated parameters and the presence of Aa was negligible in the present RA cohort. Full article

(This article belongs to the Special Issue Aggregatibacter actinomycetemcomitans)

9 pages, 1646 KiB

Open AccessArticle

HBV and HCV Co-Infection in Chinese Newly Diagnosed HIV+ Subjects in 2015 and 2023: A Cross-Sectional Study

by Fangyuan Li, Yi Feng, Xiu Liu, Jingjing Hao, Dong Wang, Hongping Hu, Chang Song, Jing Hu, Quanbi Zhao, Hua Liang, Lingjie Liao, Yuhua Ruan and Hui Xing

Pathogens 2024, 13(5), 367; https://doi.org/10.3390/pathogens13050367 - 29 Apr 2024

Viewed by 315

Abstract

With shared routes of transmission, HBV and HCV co-infection are estimated to occur more in subjects with HIV. This study aimed to characterize and describe the prevalence of HBV and HCV co-infections in a cohort of newly diagnosed HIV+ subjects living in China. [...] Read more.

With shared routes of transmission, HBV and HCV co-infection are estimated to occur more in subjects with HIV. This study aimed to characterize and describe the prevalence of HBV and HCV co-infections in a cohort of newly diagnosed HIV+ subjects living in China. We conducted a cross-sectional study among newly diagnosed HIV+ subjects aged 18–100 who participated in surveys on the national HIV molecular epidemiology in 2015 and 2023. (The epidemiological table survey is located in the national database alongside serologic testing). The chi-square test was used to identify changes in infections between the studying populations in 2015 and 2023, and conditional logistic regression models were fit to identify risk factors for each co-infection. Among the 11,024 newly diagnosed HIV+ subjects who were surveyed (n = 4501 in 2015; n = 6523 in 2023), the prevalence of HBV, HCV, and HBV/HCV in 2023 was lower than that in 2015, respectively. No decrease was observed in HCV co-infection in men who had sex with men (MSM) in North China, Northeast China, and East China. Increasing recognition among those at high risk of heterosexual transmission and those with low educational backgrounds is paramount to the prevention and control of HIV/HBV/HCV infections. Full article

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6 pages, 202 KiB

Open AccessCommunication

Application of Skimmed-Milk Flocculation Method for Wastewater Surveillance of COVID-19 in Kathmandu, Nepal

by Sarmila Tandukar, Ocean Thakali, Ananda Tiwari, Rakshya Baral, Bikash Malla, Eiji Haramoto, Jivan Shakya, Reshma Tuladhar, Dev Raj Joshi, Bhawana Sharma, Bhushan Raj Shrestha and Samendra P. Sherchan

Pathogens 2024, 13(5), 366; https://doi.org/10.3390/pathogens13050366 - 29 Apr 2024

Viewed by 435

Abstract

Wastewater surveillance (WS) has been used globally as a complementary tool to monitor the spread of coronavirus disease 2019 (COVID-19) throughout the pandemic. However, a concern about the appropriateness of WS in low- and middle-income countries (LMICs) exists due to low sewer coverage [...] Read more.

Wastewater surveillance (WS) has been used globally as a complementary tool to monitor the spread of coronavirus disease 2019 (COVID-19) throughout the pandemic. However, a concern about the appropriateness of WS in low- and middle-income countries (LMICs) exists due to low sewer coverage and expensive viral concentration methods. In this study, influent wastewater samples (n = 63) collected from two wastewater treatment plants (WWTPs) of the Kathmandu Valley between March 2021 and February 2022 were concentrated using the economical skimmed-milk flocculation method (SMFM). The presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was tested by qPCR using assays that target the nucleocapsid (N) and envelope (E) genes. Overall, 84% (53/63) of the total samples were positive for SARS-CoV-2 according to at least one of the tested assays, with concentrations ranging from 3.5 to 8.3 log₁₀ gene copies/L, indicating the effectiveness of the SMFM. No correlation was observed between the total number of COVID-19 cases and SARS-CoV-2 RNA concentrations in wastewater collected from the two WWTPs (p > 0.05). This finding cautions the prediction of future COVID-19 waves and the estimation of the number of COVID-19 cases based on wastewater concentration in settings with low sewer coverage by WWTPs. Future studies on WS in LMICs are recommended to be conducted by downscaling to sewer drainage, targeting a limited number of houses. Overall, this study supports the notion that SMFM can be an excellent economical virus-concentrating method for WS of COVID-19 in LMICs. Full article

(This article belongs to the Special Issue Emerging Viruses: Epidemiology and Surveillance Challenge)

15 pages, 5334 KiB

Open AccessArticle

Probable Role of Type IV Pili of Aeromonas hydrophila in Human Pathogenicity

by Agradip Bhattacharyya, Goutam Banerjee and Pritam Chattopadhyay

Pathogens 2024, 13(5), 365; https://doi.org/10.3390/pathogens13050365 - 28 Apr 2024

Viewed by 289

Abstract

Background: Aeromonas hydrophila is a widely recognized broad-spectrum pathogen that primarily targets the gastrointestinal tract. Type IV pili (T4P) are proteinaceous nano-machines located on the bacterial cell surface, playing a crucial role in host colonization and infection. Regrettably, the T4P systems of A. [...] Read more.

Background: Aeromonas hydrophila is a widely recognized broad-spectrum pathogen that primarily targets the gastrointestinal tract. Type IV pili (T4P) are proteinaceous nano-machines located on the bacterial cell surface, playing a crucial role in host colonization and infection. Regrettably, the T4P systems of A. hydrophila remain largely underexplored. Methods: A. hydrophila genomes with complete genome assembly and annotation reports up to March 31, 2023, were obtained from the NCBI Genome database or KEGG genome database, followed by a global search for T4P secretion system genes. Protein sequences of these manually curetted genes were used as secondary quarry for Synteny analysis. Protein–protein interaction analysis was performed by string analysis and in silico study of genomic islands. Results: We identified 27 orthologs of type IV pili (T4P) nano-machine components in A. hydrophila. These orthologs are primarily distributed across three operons: pilABCD, pilMNOPQ, and pilVWXY. While the first two operons are commonly found in all experimental genomes, the presence of the pilVWXY operon, coding for 11 orthologs, is reported here for the first time in A. hydrophila. Notably, the complete pilVWXY operon is absent in nonvirulent strains. A genomic islands study between a nonvirulent and hypervirulent strain also confirms absence of most of the genes coded by pilVWXY in nonvirulent strain. Interestingly, among the 51 experimental genomes analyzed, the pilVWXY operon was completely absent in 10 strains, most of which are categorized as nonvirulent; Conclusions: The distribution of two major type IV pili (T4P) nano-machines, PilABCDMNOPQ and PilVWXY, is reported here for the first time in A. hydrophila. Additionally, this study suggests a potential role for the PilVWXY nano-machine in establishing human disease. Full article

(This article belongs to the Section Bacterial Pathogens)

14 pages, 1152 KiB

Open AccessReview

The Role of Prevotella species in Female Genital Tract Infections

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

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

Viewed by 451

Abstract

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

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

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22 pages, 5093 KiB

Open AccessArticle

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

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

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

Viewed by 440

Abstract

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

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

(This article belongs to the Section Parasitic Pathogens)

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20 pages, 1888 KiB

Open AccessReview

Hepatitis Delta Virus and Hepatocellular Carcinoma

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

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

Viewed by 269

Abstract

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

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

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

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10 pages, 426 KiB

Open AccessArticle

Biological Control of Escherichia coli O157:H7 in Dairy Manure-Based Compost Using Competitive Exclusion Microorganisms

by Xiuping Jiang and Jingxue Wang

Pathogens 2024, 13(5), 361; https://doi.org/10.3390/pathogens13050361 - 27 Apr 2024

Viewed by 360

Abstract

Background: Animal manure-based compost is a valuable organic fertilizer and biological soil amendment. To ensure the microbiological safety of compost products, the effectiveness of competitive exclusion microorganisms (CE) in reducing Escherichia coli O157:H7 in dairy manure-based compost was evaluated. Methods: A cocktail of [...] Read more.

Background: Animal manure-based compost is a valuable organic fertilizer and biological soil amendment. To ensure the microbiological safety of compost products, the effectiveness of competitive exclusion microorganisms (CE) in reducing Escherichia coli O157:H7 in dairy manure-based compost was evaluated. Methods: A cocktail of E. coli O157:H7 strains were inoculated into dairy compost along with CE strains isolated from compost, and the reduction in E. coli O157:H7 by CE was determined in compost with 20%, 30%, and 40% moisture levels at 22 °C and 30 °C under laboratory conditions, as well as in fall, winter, and summer seasons under greenhouse settings. Results: Under lab conditions, CE addition resulted in 1.1–3.36 log reductions in E. coli O157:H7 in compost, with enhanced pathogen reduction by higher moisture and lower temperature. In the greenhouse, >99% of the E. coli O157:H7 population in compost with ≥30% moisture due to cross-contamination can be effectively inactivated by CE within 2 days during colder seasons. However, it took ≥8 days to achieve the same level of reduction for heat-adapted E. coli O157:H7 cells. Conclusions: Our results demonstrated that the competitive exclusion of microorganisms can be an effective tool for controlling foodborne pathogens in compost and reducing the potential for soil and crop contamination. Full article

(This article belongs to the Section Bacterial Pathogens)

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18 pages, 3165 KiB

Open AccessArticle

Epidemiology of Hepatitis C Virus in HIV Patients from West Mexico: Implications for Controlling and Preventing Viral Hepatitis

by Alexis Jose-Abrego, Maria E. Trujillo-Trujillo, Saul Laguna-Meraz, Sonia Roman and Arturo Panduro

Pathogens 2024, 13(5), 360; https://doi.org/10.3390/pathogens13050360 - 27 Apr 2024

Viewed by 279

Abstract

The complex epidemiology of hepatitis C virus (HCV) infection among human immunodeficiency virus (HIV) patients in West Mexico remains poorly understood. Thus, this study aimed to investigate the HCV prevalence, HCV-associated risk factors, and HCV genotypes/subtypes and assess their impacts on liver fibrosis [...] Read more.

The complex epidemiology of hepatitis C virus (HCV) infection among human immunodeficiency virus (HIV) patients in West Mexico remains poorly understood. Thus, this study aimed to investigate the HCV prevalence, HCV-associated risk factors, and HCV genotypes/subtypes and assess their impacts on liver fibrosis in 294 HIV patients (median age: 38 years; 88.1% male). HCV RNA was extracted and amplified by PCR. Hepatic fibrosis was assessed using three noninvasive methods: transient elastography (TE), the aspartate aminotransferase (AST)-to-platelets ratio index score (APRI), and the fibrosis-4 score (FIB4). Patients with liver stiffness of ≥9.3 Kpa were considered to have advanced liver fibrosis. HCV genotypes/subtypes were determined by line probe assay (LiPA) or Sanger sequencing. The prevalence of HIV/HCV infection was 36.4% and was associated with injection drug use (odds ratio (OR) = 13.2; 95% confidence interval (CI) = 5.9–33.6; p < 0.001), imprisonment (OR = 3.0; 95% CI = 1.7–5.4; p < 0.001), the onset of sexual life (OR = 2.6; 95% CI = 1.5–4.5; p < 0.001), blood transfusion (OR = 2.5; 95% CI = 1.5–4.2; p = 0.001), tattooing (OR = 2.4; 95% CI = 1.4–3.9; p = 0.001), being a sex worker (OR = 2.3; 95% CI = 1.0–5.4; p = 0.046), and surgery (OR = 1.7; 95% CI = 1.0–2.7; p = 0.042). The HCV subtype distribution was 68.2% for 1a, 15.2% for 3a, 10.6% for 1b, 3.0% for 2b, 1.5% for 2a, and 1.5% for 4a. The advanced liver fibrosis prevalence was highest in patients with HIV/HCV co-infection (47.7%), especially in those with HCV subtype 1a. CD4+ counts, albumin, direct bilirubin, and indirect bilirubin were associated with liver fibrosis. In conclusion, HCV infection had a significant impact on the liver health of Mexican HIV patients, highlighting the need for targeted preventive strategies in this population. Full article

(This article belongs to the Special Issue Elimination Strategies for Viral Hepatitis in Latin America)

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12 pages, 269 KiB

Open AccessArticle

Detectable Virological Load and Associated Factors among People Living with HIV on Antiretroviral Treatment: A Retrospective Study

by Pierpaolo Congedo, Raffaella Sedile, Marcello Guido, Federico Banchelli and Antonella Zizza

Pathogens 2024, 13(5), 359; https://doi.org/10.3390/pathogens13050359 - 27 Apr 2024

Viewed by 394

Abstract

The complete and prolonged suppression of viral load is the primary objective of HAART in people living with HIV. Some people may experience therapeutic failure, while others may achieve virological suppression but are unable to maintain it, developing persistent or single detection of [...] Read more.

The complete and prolonged suppression of viral load is the primary objective of HAART in people living with HIV. Some people may experience therapeutic failure, while others may achieve virological suppression but are unable to maintain it, developing persistent or single detection of low-level viremia. This study aims to evaluate the determinants of a detectable viral load among patients on HAART to identify and address them promptly. In this retrospective study, all patients referring to the Infectious Disease Operative Unit of the Vito Fazzi Hospital in Lecce, Puglia, older than 18 years, receiving HAART for at least 12 months as of 30 June 2022, were included. For each patient, demographic characteristics such as age, sex, educational level, stable relationship, cohabitation, employment status, and information relating to habits and lifestyles such as physical activity, use of drugs, and substances or supplements for sport, abuse of alcohol, and smoking were collected. Degree of comorbidity was quantified according to the Charlson Comorbidity Index, and the presence of obesity and the COVID-19 infection was also considered. Univariable and multivariable logistic regression models were used to assess the association between patients’ characteristics and the outcome. In the multivariable logistic regression model, the odds were lower for the duration of therapy (OR: 0.96; p = 0.0397), prescriber’s perception of adherence to therapy (OR: 0.50; p < 0.0001), and Nadir CD4+ T-cell count (OR: 0.85; p = 0.0329), and higher for the presence of AIDS (OR: 1.89; p = 0.0423) and COVID-19 (OR: 2.31; p = 0.0182). Our findings support the early initiation of HAART to achieve virological suppression. Additionally, measures to improve adherence to therapy should be adopted to ensure better outcomes for patients. Full article

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

15 pages, 5716 KiB

Open AccessArticle

Assessment of Drug Activities against Giardia Using Hyperspectral Raman Microscopy

by Felicia S. Manciu, Jose Guerrero, Breanna C. Pence, Lizbeth V. Martinez Lopez and Siddhartha Das

Pathogens 2024, 13(5), 358; https://doi.org/10.3390/pathogens13050358 - 27 Apr 2024

Viewed by 370

Abstract

This study demonstrates the capability of Raman microscopy for detecting structural differences in Giardia cells exposed to different drugs and incubation times. While metronidazole (MTZ) visibly affects the cells by inducing extracellular vesicle releases of toxic iron intermediates and modified triple-bond moieties, oseltamivir [...] Read more.

This study demonstrates the capability of Raman microscopy for detecting structural differences in Giardia cells exposed to different drugs and incubation times. While metronidazole (MTZ) visibly affects the cells by inducing extracellular vesicle releases of toxic iron intermediates and modified triple-bond moieties, oseltamivir (OSM) alters the phenylalanine and lipid structures. Modifications in the heme protein environment and the transformation of iron from ferric to ferrous observed for both drug treatments are more notable for MTZ. Different contents and amounts of vesicle excretion are detected for 24 h or 48 h with MTZ incubation. At a shorter drug exposure, releases of altered proteins, glycogen, and phospholipids dominate. Agglomerates of transformed iron complexes from heme proteins and multiple-bond moieties prevail at 48 h of treatment. No such vesicle releases are present in the case of OSM usage. Drug incorporations into the cells and their impact on the plasma membrane and the dynamics of lipid raft confirmed by confocal fluorescence microscopy reveal a more destructive extent by OSM, corroborating the Raman results. Raman microscopy provides a broader understanding of the multifaceted factors and mechanisms responsible for giardiasis treatment or drug resistance by enabling a label-free, simultaneous monitoring of structural changes at the cellular and molecular levels. Full article

(This article belongs to the Special Issue Pathogenesis and Treatment of Giardiasis)

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22 pages, 2920 KiB

Open AccessReview

Gastric Cancer, Immunotherapy, and Nutrition: The Role of Microbiota

by Pauline Raoul, Valeria De Gaetano, Gianmario Sciaraffia, Ginevra Ormea, Marco Cintoni, Carmelo Pozzo, Antonia Strippoli, Antonio Gasbarrini, Maria Cristina Mele and Emanuele Rinninella

Pathogens 2024, 13(5), 357; https://doi.org/10.3390/pathogens13050357 - 26 Apr 2024

Viewed by 255

Abstract

Immune checkpoint inhibitors (ICI) have revolutionized the treatment of gastric cancer (GC), which still represents the third leading cause of cancer-related death in Western countries. However, ICI treatment outcomes vary between individuals and need to be optimized. Recent studies have shown that gut [...] Read more.

Immune checkpoint inhibitors (ICI) have revolutionized the treatment of gastric cancer (GC), which still represents the third leading cause of cancer-related death in Western countries. However, ICI treatment outcomes vary between individuals and need to be optimized. Recent studies have shown that gut microbiota could represent a key influencer of immunotherapy responses. At the same time, the nutritional status and diet of GC patients are also predictive of immunotherapy treatment response and survival outcomes. The objective of this narrative review is to gather recent findings about the complex relationships between the oral, gastric, and gut bacterial communities, dietary factors/nutritional parameters, and immunotherapy responses. Perigastric/gut microbiota compositions/functions and their metabolites could be predictive of response to immunotherapy in GC patients and even overall survival. At the same time, the strong influence of diet on the composition of the microbiota could have consequences on immunotherapy responses through the impact of muscle mass in GC patients during immunotherapy. Future studies are needed to define more precisely the dietary factors, such as adequate daily intake of prebiotics, that could counteract the dysbiosis of the GC microbiota and the impaired nutritional status, improving the clinical outcomes of GC patients during immunotherapy. Full article

(This article belongs to the Special Issue Gut Microbiome: Current Status and Future Perspectives)

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21 pages, 2446 KiB

Open AccessArticle

Investigation of Potential Gut Health Biomarkers in Broiler Chicks Challenged by Campylobacter jejuni and Submitted to a Continuous Water Disinfection Program

by Tilemachos Mantzios, Despoina E. Kiousi, Georgia D. Brellou, Georgios A. Papadopoulos, Vangelis Economou, Marili Vasilogianni, Elisavet Kanari, Evanthia Petridou, Ilias Giannenas, Guillermo Tellez-Isaias, Aglaia Pappa, Alex Galanis and Vasilios Tsiouris

Pathogens 2024, 13(5), 356; https://doi.org/10.3390/pathogens13050356 - 26 Apr 2024

Viewed by 540

Abstract

The exploration of novel biomarkers to assess poultry health is of paramount importance, not only to enhance our understanding of the pathogenicity of zoonotic agents but also to evaluate the efficacy of novel treatments as alternatives to antibiotics. The present study aimed to [...] Read more.

The exploration of novel biomarkers to assess poultry health is of paramount importance, not only to enhance our understanding of the pathogenicity of zoonotic agents but also to evaluate the efficacy of novel treatments as alternatives to antibiotics. The present study aimed to investigate potential gut health biomarkers in broiler chicks challenged by Campylobacter jejuni and subjected to a continuous water disinfection program. A total of 144 one-day-old hatched broiler chicks were randomly allocated to four treatment groups with four replicates each, according to the following experimental design: Group A received untreated drinking water; Group B received drinking water treated with 0.01–0.05% v/v Cid 2000™ (hydrogen peroxide, acetic acid and paracetic acid); Group C was challenged by C. jejuni and received untreated drinking water; and Group D was challenged by C. jejuni and received drinking water treated with 0.01–0.05% v/v Cid 2000™. The use of Cid 2000™ started on day 1 and was applied in intervals until the end of the experiment at 36 days, while the C. jejuni challenge was applied on day 18. Potential biomarkers were investigated in serum, feces, intestinal tissue, intestinal content, and liver samples of broilers. Statistical analysis revealed significant increases (p < 0.001) in serum cortisol levels in C. jejuni-challenged broilers. Serum fluorescein isothiocyanate dextran (FITC-d) increased significantly (p = 0.004) in broilers challenged by C. jejuni and treated with drinking water disinfectant, while fecal ovotransferrin concentration also increased significantly (p < 0.001) in broilers that received the drinking water disinfectant alone. The gene expression levels of occludin (p = 0.003) and mucin-2 (p < 0.001) were significantly upregulated in broilers challenged by C. jejuni, while mucin-2 significantly increased in birds that were challenged and received the drinking water disinfectant (p < 0.001). TLR-4 expression levels were significantly (p = 0.013) decreased in both groups that received the drinking water disinfectant, compared to the negative control group. Finally, the C. jejuni challenge significantly increased (p = 0.032) the crypt depth and decreased (p = 0.021) the villus height-to-crypt-depth ratio in the ileum of birds, while the tested disinfectant product increased (p = 0.033) the villus height in the jejunum of birds. Furthermore, the counts of C. jejuni in the ceca of birds (p = 0.01), as well as its translocation rate to the liver of broilers (p = 0.001), were significantly reduced by the addition of the water disinfectant. This research contributes to novel insights into the intricate interplay of water disinfection and/or C. jejuni challenge with potential intestinal biomarkers. In addition, it emphasizes the need for continued research to unveil the underlying mechanisms, expands our understanding of broiler responses to these challenges and identifies breakpoints for further investigations. Full article

(This article belongs to the Special Issue Molecular Detection and Surveillance of Veterinary Infectious Disease)

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11 pages, 571 KiB

Open AccessCommunication

A Proof-of-Concept Protein Microarray-Based Approach for Serotyping of Salmonella enterica Strains

by Sascha D. Braun, Elke Müller, Katrin Frankenfeld, Dominik Gary, Stefan Monecke and Ralf Ehricht

Pathogens 2024, 13(5), 355; https://doi.org/10.3390/pathogens13050355 - 25 Apr 2024

Viewed by 379

Abstract

Salmonella enterica, a bacterium causing foodborne illnesses like salmonellosis, is prevalent in Europe and globally. It is found in food, water, and soil, leading to symptoms like diarrhea and fever. Annually, it results in about 95 million cases worldwide, with increasing antibiotic [...] Read more.

Salmonella enterica, a bacterium causing foodborne illnesses like salmonellosis, is prevalent in Europe and globally. It is found in food, water, and soil, leading to symptoms like diarrhea and fever. Annually, it results in about 95 million cases worldwide, with increasing antibiotic resistance posing a public health challenge. Therefore, it is necessary to detect and serotype Salmonella for several reasons. The identification of the serovars of Salmonella enterica isolates is crucial to detect and trace outbreaks and to implement effective control measures. Our work presents a protein-based microarray for the rapid and accurate determination of Salmonella serovars. The microarray carries a set of antibodies that can detect different Salmonella O- and H-antigens, allowing for the identification of multiple serovars, including Typhimurium and Enteritidis, in a single miniaturized assay. The system is fast, economical, accurate, and requires only small sample volumes. Also, it is not required to maintain an extensive collection of sera for the serotyping of Salmonella enterica serovars and can be easily expanded and adapted to new serovars and sera. The scientific state of the art in Salmonella serotyping involves the comparison of traditional, molecular, and in silico methods, with a focus on economy, multiplexing, accuracy, rapidity, and adaptability to new serovars and sera. The development of protein-based microarrays, such as the one presented in our work, contributes to the ongoing advancements in this field. Full article

(This article belongs to the Special Issue New Approaches to Combating Multidrug-Resistant Pathogens)

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11 pages, 1569 KiB

Open AccessReview

Therapeutic Applications of Aggregatibacter actinomycetemcomitans Leukotoxin

by Scott C. Kachlany and Brian A. Vega

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

Viewed by 257

Abstract

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

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

(This article belongs to the Special Issue Aggregatibacter actinomycetemcomitans)

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Open AccessReply

Reply to Shah, J.S.; Ramasamy, R. Target Antigens in Western and Line Immunoblots for Supporting the Diagnosis of Lyme Disease. Comment on “Porwancher et al. Immunoblot Criteria for Diagnosis of Lyme Disease: A Comparison of CDC Criteria to Alternative Interpretive Approaches. Pathogens 2023, 12, 1282”

by Richard Porwancher, Andrew Levin and Rosalie Trevejo

Pathogens 2024, 13(5), 353; https://doi.org/10.3390/pathogens13050353 - 25 Apr 2024

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Abstract

We are writing in response to comments made by Shah and Ramasamy [...] Full article

(This article belongs to the Special Issue Pathogenesis, Epidemiology, Host Response and Control of Lyme Disease and Other Tick-Borne Diseases)

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Pathogens, Volume 13, Issue 5 (May 2024) – 34 articles

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