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Pathogens
Volume 13
Issue 8
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Pathogens, Volume 13, Issue 8 (August 2024) – 105 articles

Cover Story (view full-size image): Intestinal parasitic infection greatly impacts health on both an individual and global scale. Within the gastrointestinal tract, dealing with incoming parasites requires a delicate balance, and it is becoming increasingly apparent that interactions, not only between host and parasite, but also between host, parasite and resident microbes, help dictate outcomes in parasitic infection. In this review, we explore the relationship between intestinal parasites, with a particular focus on common protozoa and helminths, and the gut microbiota, and how these interactions can influence host defense and intestinal immune response. We will also explore the impact of this tripartite relationship in a clinical setting and its broader implications for human health. View this paper
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13 pages, 6148 KiB  
Article
In Vivo Evaluation of Sepigel-Based Meglumine Antimoniate and Amphotericin B for Cutaneous Leishmaniasis Treatment
by Atteneri López-Arencibia, Carlos J. Bethencourt-Estrella, Diana Berenguer, Angélica Domínguez-de-Barros, M. Magdalena Alcover, Marcella Sessa, Lyda Halbaut, Roser Fisa, Ana Cristina Calpena-Campmany, A. Elizabeth Córdoba-Lanús, Jacob Lorenzo-Morales, Cristina Riera and José E. Piñero
Pathogens 2024, 13(8), 712; https://doi.org/10.3390/pathogens13080712 - 22 Aug 2024
Viewed by 521
Abstract
Cutaneous leishmaniasis (CL) poses a significant public health concern in endemic regions due to its increasing prevalence and substantial impact on affected individuals. This disease is primarily caused by the Leishmania protozoa, which are transmitted through insect bites, and it manifests as a [...] Read more.
Cutaneous leishmaniasis (CL) poses a significant public health concern in endemic regions due to its increasing prevalence and substantial impact on affected individuals. This disease is primarily caused by the Leishmania protozoa, which are transmitted through insect bites, and it manifests as a range of symptoms, from self-healing lesions to severe disfigurement. Current treatments, which often involve the parenteral administration of antimonials, face challenges such as poor compliance and adverse effects. This study investigates the efficacy of topical formulations containing meglumine antimoniate (MA) and amphotericin B (AmB), using Sepigel as an excipient, for treating CL. In the in vivo study, BALB/c mice infected with L. amazonensis developed lesions at the injection site five weeks post-infection. Subsequently, the mice were divided into eight groups: untreated mice, mice treated orally with miltefosine, mice treated intraperitoneally with MA, and mice treated topically with 15%, 22.5%, and 30% MA-Sepigel, as well as those treated with AmB-Sepigel. Treatments were applied daily for two weeks, and the results revealed a significant reduction in lesion size and parasite burden following topical application, particularly with the AmB-Sepigel formulations and 30% MA-Sepigel. Additionally, Sepigel-based treatments demonstrated improved patient compliance and reduced toxicity compared to systemic therapies. These findings underscore the potential of Sepigel-based formulations as a promising alternative for CL treatment. They offer enhanced efficacy and tolerability, while reducing the systemic toxicity associated with conventional therapies. Full article
(This article belongs to the Special Issue Opportunistic and Rare Parasitic Infections)
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Figure 1

Figure 1
<p>Chemical structure of MA (<b>A</b>), miltefosine (<b>B</b>), and AmB (<b>C</b>).</p> Full article ">Figure 2
<p>Scheme of treatment procedures used for the <span class="html-italic">in vivo</span> experiments. Blue arrows indicate the timeline of lesion measurement.</p> Full article ">Figure 3
<p>Efficacy of control treatments on CL lesions. Each row corresponds to a different treatment along the time. (<b>A</b>–<b>D</b>) without treatment; (<b>E</b>–<b>H</b>) oral miltefosine; (<b>I</b>–<b>L</b>) intraperitoneal MA; (<b>M</b>–<b>P</b>) topical Sepigel. Each column corresponds to a point in time: (<b>A</b>,<b>E</b>,<b>I</b>,<b>M</b>) shows the dimension of the CL lesions before treatment; (<b>B</b>,<b>F</b>,<b>J</b>,<b>N</b>) shows the dimension of the CL lesions after treatment (week 2); (<b>C</b>,<b>G</b>,<b>K</b>,<b>O</b>) shows the dimension of the CL lesions two weeks after treatment (week 4); (<b>D</b>,<b>H</b>,<b>L</b>,<b>P</b>) shows the dimension of the CL lesions four weeks after treatment (week 6).</p> Full article ">Figure 4
<p>Efficacy of Sepigel-treatments on CL lesions. Each row corresponds to a different treatment along the time. (<b>A</b>–<b>D</b>) 15% MA-Sepigel; (<b>E</b>–<b>H</b>) 22.5% MA-Sepigel; (<b>I</b>–<b>L</b>) 30% MA-Sepigel; (<b>M</b>–<b>P</b>) AmB-Sepigel. Each column corresponds to a point in time. (<b>A</b>,<b>E</b>,<b>I</b>,<b>M</b>) shows the dimension of the CL lesions before treatment; (<b>B</b>,<b>F</b>,<b>J</b>,<b>N</b>) shows the dimension of the CL lesions after treatment (week 2); (<b>C</b>,<b>G</b>,<b>K</b>,<b>O</b>) shows the dimension of the CL lesions two weeks after treatment (week 4); (<b>D</b>,<b>H</b>,<b>L</b>,<b>P</b>) shows the dimension of the CL lesions four weeks after treatment (week 6).</p> Full article ">Figure 5
<p>Progression of lesion size in <span class="html-italic">L. amazonensis</span> infected BALB/c mice treated with different concentrations of topical Sepigel-based treatments. Lesion size was measured in two dimensions using calipers, and the mean lesion diameters were determined. Lesions were treated topically with 50 µL of the formulations once daily for 2 weeks. Lesion size was recorded during treatment and up to 4 weeks after the end of treatment. w/t: without treatment; Oral milte: oral miltefosine; Int MA: intraperitoneally injected MA; MA: meglumine antimoniate; AmB: amphotericin B. a/t: after treatment. N = 4. * <span class="html-italic">p</span> &lt; 0.05; ** <span class="html-italic">p</span> &lt; 0.01; *** <span class="html-italic">p</span> &lt; 0.001; **** <span class="html-italic">p</span> &lt; 0.0001. All treatments evaluated at 3 weeks a/t and 4 weeks a/t showed <span class="html-italic">p</span> &lt; 0.0001 with respect to the untreated control.</p> Full article ">Figure 6
<p>Skin and liver parasite burden in BALB/c mice from control and experimental groups. The number of <span class="html-italic">L. amazonensis</span> was quantified using qPCR from tissue of (<b>A</b>) skin (lesion edge) and (<b>B</b>) liver tissue from the different groups of mice at week 4 after the end of treatment. w/t: without treatment; Oral milte: oral miltefosine; Inj MA: intraperitoneally injected MA; MA: meglumine antimoniate in Sepigel; AmB: amphotericin B in Sepigel. N = 4. * <span class="html-italic">p</span> &lt; 0.05; *** <span class="html-italic">p</span> &lt; 0.001.</p> Full article ">
9 pages, 2050 KiB  
Article
The Structural Framework and Opening Appearance of the VP1-Pocket of Enteroviruses Correlated with Viral Thermostability
by Xiaojing Lin, Jianhong Gan, Qiang Sun, Zi Li, Kun Qin, Yong Zhang, Yang Cao and Jianfang Zhou
Pathogens 2024, 13(8), 711; https://doi.org/10.3390/pathogens13080711 - 22 Aug 2024
Viewed by 407
Abstract
Enteroviruses (EVs and RVs) are prevalent worldwide and cause various diseases in humans, of which the VP1-pocket is a target of antivirals, with a lipid molecule as a pocket factor to stabilize the virion. However, the characterization of the structure of the VP1-pocket [...] Read more.
Enteroviruses (EVs and RVs) are prevalent worldwide and cause various diseases in humans, of which the VP1-pocket is a target of antivirals, with a lipid molecule as a pocket factor to stabilize the virion. However, the characterization of the structure of the VP1-pocket in EVs is poor. Here, we compared the published capsid crystals of EVs and RVs and proposed a structural framework for the VP1-pocket: Frame 1–4, which is located at the CD loop, GH loop, and C-terminus, presenting with an outward opening appearance or not. The non-outward viral strains—CVB3, Echo 11, RV-A81, and RV-B70—are more thermally stable, with a breakpoint temperature (B.T.) of 51~62 °C for genome releasing, which is 4~10 °C higher than its outward temperature of 41~47 °C, and infectivity preservation when treated at 50 °C for 3 min. Its outward versus non-outward opening is correlated significantly with the B.T. for genome release (r = −0.90; p = 0.0004) and infectivity (r = −0.82, p = 0.0039). The energy of Frames 1, 2, and 4, including Van der Waals attractive and repulsive interactions and hydrogen bonds, showed significant correlations with the B.T. (r = −0.67, 0.75, and −0.8; p = 0.034, 0.013, and 0.006, respectively). These characters of the VP1-pocket could be predictors for virion thermostability and aid in the development of vaccines or antivirals. Full article
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Figure 1

Figure 1
<p>Structural analysis of the VP1-pocket opening of EVs and RVs. (<b>A</b>) Capsid protein VP1 shown in cartoon, representing the pocket factor in yellow. (<b>B</b>) Scheme of capsid protein VP1. The pocket opening-related frame located in the connection loop between CD β-strands (denoted Frame 1) and GH β-strands (denoted as Frame 2 and Frame 3), by which Frame 1 and 2 formed the roof of the pocket outwardly on the surface while Frame 2 and 3 formed the wall of pocket buried within the pentamer. The bidirectional black arrow indicated the relative positions among Frame 1, 2, and 3. (<b>C</b>) The pentamer shown in cartoon with the pocket factor in yellow. (<b>D</b>) The pocket opening on the roof unmasking the pocket factor (EV-A71). (<b>E</b>) The pocket opening not-on-the-roof masking the pocket factor (Echo11). (<b>F</b>) Maximum distance measurement between the side chains of Frame 1 and 2, for which EV-A71, Echo 30, Poliovirus3, and EV-D68 had pocket openings on the roof, and Echo 11, RV-A16, and RV-B14 had pocket openings not-on-the-roof. (<b>G</b>) Frame displacement of the VP1-pocket from native virion to A-particle; Frames 1, 2, 3, and 4 colored in blue, red, aquamarine, and orange, respectively. VP1, VP2, and VP3 colored in green, cyan, and magenta, respectively. The black arrow indicated the opening appearance.</p> Full article ">Figure 2
<p>Thermostability of represented EVs and RVs. (<b>A</b>) Normalized fluorescence of Genome release of EVs and RVs. About 4 μg virus in a 20 μL reaction was set up at 37 °C for 15 min and subsequently the temperature was increased to 90 °C, with recordings of 10 points of fluorescence signal at 1 °C intervals. The experiment was repeated at least in duplicate. (<b>B</b>) First derivative of the Normalized Fluorescence identified the breakpoint temperature of the genome release. (<b>C</b>) Breakpoint temperature of EVs and RVs. (<b>D</b>) Fluorescence fold-change of genome release at 50 °C for 3, 10, 20, 30, and 40 min compared that at 0 min. The reaction set-up was the same as described previously. (<b>E</b>) The Normalized fluorescence of genome release after treatment at 50 °C for 40 min. (<b>F</b>) Infectivity difference of EVs and RVs treated at 50 °C for 3 min compared to 0 min (without 50 °C treatment). The experiment was repeated at least in triplicate. Statistical analysis was performed by one-way ANOVA with multiple comparisons. ** indicates <span class="html-italic">p</span> &lt; 0.01 and **** indicates <span class="html-italic">p</span> &lt; 0.0001. (<b>G</b>) Correlation of Log<sub>10</sub>TCID<sub>50</sub> and breakpoint temperature (Pearson’s <span class="html-italic">r</span> = 0.77, <span class="html-italic">p</span> = 0.009). (<b>H</b>) Correlation of the pocket opening with breakpoint temperature (Pearson’s <span class="html-italic">r</span> = −0.90, <span class="html-italic">p</span> = 0.0004) and Log<sub>10</sub>TCID<sub>50</sub> reduction post-50 °C treatment (Pearson’s <span class="html-italic">r</span> = −0.82, <span class="html-italic">p</span> = 0.0039) with linear regression.</p> Full article ">
12 pages, 1029 KiB  
Article
One Health Priorities: Advancing Veterinary Public Health in Latin America and the Caribbean
by Felipe Rocha, Alessandra Cristiane Sibim, Baldomero Molina-Flores, Wagner Antonio Chiba de Castro, Louise Bach Kmetiuk, Renato Vieira Alves, André Luis de Sousa dos Santos, Margarita Corrales Moreno, Álvaro A. Faccini-Martínez, Natalia Margarita Cediel, Alexander Welker Biondo, Ottorino Cosivi and Marco Antonio Natal Vigilato
Pathogens 2024, 13(8), 710; https://doi.org/10.3390/pathogens13080710 - 21 Aug 2024
Viewed by 981
Abstract
One Health (OH) is an integrative approach to human, animal, and environmental health and can be used as a comprehensive indicator for comparative purposes. Although an OH index has been proposed for comparing cities, states, and countries, to date, no practical study has [...] Read more.
One Health (OH) is an integrative approach to human, animal, and environmental health and can be used as a comprehensive indicator for comparative purposes. Although an OH index has been proposed for comparing cities, states, and countries, to date, no practical study has compared countries using this approach. Accordingly, this study aimed to assess OH initiatives using a survey with a veterinary public health focus. The questionnaire contained 104 quantitative questions and was sent to representatives of governmental institutions of 32 countries in the Americas. After exclusion criteria were considered, a total of 35 questionnaires from 17 countries were analyzed, with country names remaining undisclosed during the statistical analyses to protect potentially sensitive information. Principal component analysis (PCA) of health parameters in Latin America and the Caribbean (LAC) as a function of country perception (self-vector) showed that food safety was ranked higher than public policies (p = 0.009), and that both (p = 0.003) were ranked higher than institutional routines related to zoonosis programs. National policies in accordance with international standards, regulations, recommendations, and guidelines was considered the standout topic for public policy, with higher-ranking topics including standard. Meanwhile, challenging topics included tools, preparedness, governance, and research. Food safety showed both strengths and challenges in the coordination of its activities with other sectors. Food safety communication was scored as a strength, while foodborne diseases prevention was ranked as a challenge. Institutional routines for zoonosis maintained both strong and challenging topics in the execution and implementation of attributions and daily routine. Thus, the survey showed that topics such as access to and compliance with international guidelines and intercountry integration were ranked higher than in-country articulation, particularly among food safety, zoonoses, and environmental institutions. Full article
(This article belongs to the Special Issue One Health and Neglected Zoonotic Diseases)
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<p>Countries participating in the One Health perception questionnaire.</p> Full article ">Figure 2
<p>Graphic of principal component analysis showing the One Health perceptions of Latin American and Caribbean countries (17 self-vectors), with a focus on veterinary public health, based on the applied questionnaire (<a href="#app1-pathogens-13-00710" class="html-app">Supplementary Table S1</a>). Colors indicate the veterinary public health parameters and ellipses indicate the confidence intervals (food safety in red, institutional routines for zoonosis in green, and public policy in blue).</p> Full article ">
12 pages, 1533 KiB  
Article
Quality Control of Microscopic Diagnosis of Malaria in Healthcare Facilities and Submicroscopic Infections in Mossendjo, the Department of Niari, the Republic of the Congo
by Grâce Petula Urielle Fila-Fila, Felix Koukouikila-Koussounda, Fabien Roch Niama, Lauriate Prudencie Bissombolo Madingou, Jordy Exaucé Demboux, Aldi Fred Mandiangou, Stéphane Vembe Mahounga, Ahmed Jordy Doniama, Louis Régis Dossou-Yovo, Prisca Nadine Casimiro and Pembe Issamou Mayengue
Pathogens 2024, 13(8), 709; https://doi.org/10.3390/pathogens13080709 - 21 Aug 2024
Viewed by 524
Abstract
The control and management of malaria are linked to the quality of diagnosis. We sought to estimate the performance of routine microscopy for malaria diagnosis and assess the prevalence of submicroscopic Plasmodium (P.) falciparum infection among febrile patients in two healthcare [...] Read more.
The control and management of malaria are linked to the quality of diagnosis. We sought to estimate the performance of routine microscopy for malaria diagnosis and assess the prevalence of submicroscopic Plasmodium (P.) falciparum infection among febrile patients in two healthcare facilities in Mossendjo, the Republic of the Congo. A cross-sectional study was conducted between January and December 2022. A total of 650 and 234 patients with signs of uncomplicated malaria were enrolled at the Centre de Sante Intégré (CSIMSJ) and Hôpital de Base (HBMSJ), respectively. Two thick blood smears were performed for each patient, one analyzed by routine microscopists and the other by an expert. The msp-1 and msp-2 genes were genotyped to detect submicroscopic P. falciparum infection. At the CSIMSJ, the sensitivity was 49.5% and the specificity was 88.6%. The positive and negative predictive values were 77.7% and 68.7%, respectively. At the HBMSJ, the sensitivity was 32.9% and the specificity was 79.4%. The positive and negative predictive values were 44.8% and 69.5%, respectively. P. falciparum was the only species detected by routine microscopists, while experts identified some cases with P. malariae and P. ovale. The proportion of submicroscopic infections was 35.75%. Children under 5 years old had higher rates of parasitemia. However, submicroscopic infections were more pronounced in the adult group. The performance of routine malaria microscopists at Mossendjo was inaccurate at both sites. With the large proportion of submicroscopic infection, malaria management at Mossendjo requires the improvement of microscopists’ skills and the concomitant use of RDTs. Full article
(This article belongs to the Special Issue Epidemiology, Diagnosis and Clinical Management of Human Parasitic Infections)
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<p>The map representing the region and the different sites of this study.</p> Full article ">Figure 2
<p>Comparison of parasite density between the sites’ microscopists and the experts.</p> Full article ">Figure 3
<p>Relationship between microscopic and submicroscopic infections with age.</p> Full article ">
19 pages, 4173 KiB  
Article
Evaluation of Chemical and Biological Products for Control of Crown Gall on Rose
by Cansu Oksel, Prabha Liyanapathiranage, Madhav Parajuli, Farhat A. Avin, Christina Jennings, Terri Simmons and Fulya Baysal-Gurel
Pathogens 2024, 13(8), 708; https://doi.org/10.3390/pathogens13080708 - 21 Aug 2024
Viewed by 487
Abstract
Crown gall is a soil-borne bacterial disease caused by Agrobacterium tumefaciens, leading to significant economic losses in many plant species. For the assessment of the biological and chemical products on crown gall, each plant’s crown region and roots were wounded, and then [...] Read more.
Crown gall is a soil-borne bacterial disease caused by Agrobacterium tumefaciens, leading to significant economic losses in many plant species. For the assessment of the biological and chemical products on crown gall, each plant’s crown region and roots were wounded, and then were dipped into their respective treatments. After the treatments, the plants were inoculated with a suspension of pathogenic A. tumefaciens isolate FBG1034 and maintained in a greenhouse for six months to assess them for gall formation. A quantitative real-time PCR assay was performed to quantify the A. tumefaciens using the chvE gene. Biological products such as the Agrobacterium radiobacter strain K1026, and strains 1 and 2, resulted in the lowest average root gall diameter and significantly reduced the crown gall diameter to stem diameter ratio, and the chemical product copper octanoate reduced the number of crown and root galls as well as the crown and root gall diameter compared to the inoculated, non-treated control. Moreover, both the A. radiobacter strain K1026 and strain 1 treatments resulted in an approximately 85% and 65% reduction in crown and root gall incidence, respectively, in both of the trials compared to the inoculated, non-treated plants. The findings of this study indicate that the use of biological and chemical products could help to suppress crown and root gall disease in rose plants. Full article
(This article belongs to the Section Bacterial Pathogens)
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Figure 1
<p>Identification of the tumorigenic <span class="html-italic">A. tumefaciens</span> isolates FBG1034 and FBG1035 using biochemical tests: (<b>A</b>) pink to pinkish-red color colony on 1A medium; (<b>B</b>) Gram-negative bacteria based on the Gram staining; (<b>C</b>) in the oxidase test, the inoculated filter paper turned violet immediately after adding the reagent; (<b>D</b>) in the catalase test, bubbles were formed on the Petri plate after adding H<sub>2</sub>O<sub>2</sub>; (<b>E</b>) the isolates were not produced gelatinases; (<b>F</b>) the isolates were unable to hydrolyze starch.</p> Full article ">Figure 1 Cont.
<p>Identification of the tumorigenic <span class="html-italic">A. tumefaciens</span> isolates FBG1034 and FBG1035 using biochemical tests: (<b>A</b>) pink to pinkish-red color colony on 1A medium; (<b>B</b>) Gram-negative bacteria based on the Gram staining; (<b>C</b>) in the oxidase test, the inoculated filter paper turned violet immediately after adding the reagent; (<b>D</b>) in the catalase test, bubbles were formed on the Petri plate after adding H<sub>2</sub>O<sub>2</sub>; (<b>E</b>) the isolates were not produced gelatinases; (<b>F</b>) the isolates were unable to hydrolyze starch.</p> Full article ">Figure 2
<p>Identification of the tumorigenic <span class="html-italic">A. tumefaciens</span> isolates FBG1034 and FBG1035 using the PCR amplification of specific and universal genetic markers: (<b>A</b>) specific genus level to all tumorigenic <span class="html-italic">Agrobacterium</span> species (primers: virD2A/virD2C); (<b>B</b>) specific genus level to the <span class="html-italic">A. tumefaciens</span> biovar 1 species complex (primers: VCF/VCR); (<b>C</b>) specific genus level to the nopaline <span class="html-italic">A. tumefaciens</span> type (primers: RB-F/RB-R); (<b>D</b>) specific genus level to the agrocinopine <span class="html-italic">A. tumefaciens</span> type (primers: ACC-F/ACC-R); (<b>E</b>) ribosomal 16S universal primers (8F/1492R).</p> Full article ">Figure 3
<p>The formation of galls on the carrot slices caused by the <span class="html-italic">A. tumefaciens</span> isolates FBG1034 (<b>A</b>) and FBG1035 (<b>B</b>).</p> Full article ">Figure 4
<p>Crown (<b>A</b>) and root gall (<b>B</b>) diameters (mean ± SE) of the rose plants per treatment in the greenhouse trials. Means followed by different lowercase (trial 1) and uppercase (trial 2) letters above the bar representing the significant differences (n = 10, <span class="html-italic">p</span> ≤ 0.05, one-way ANOVA with post hoc Fisher’s test with an α = 0.05).</p> Full article ">Figure 5
<p>Number of crown (<b>A</b>) and root (<b>B</b>) galls (mean ± SE) for the rose plants per treatment in the greenhouse trials. Means followed by different lowercase (trial 1) and uppercase (trial 2) letters above the bar represent significant differences (n = 10, <span class="html-italic">p</span> ≤ 0.05, one-way ANOVA with post hoc the Fisher’s test the with an α = 0.05).</p> Full article ">Figure 6
<p>Effect of the treatments on the crown gall diameter to the stem diameter (GD/SD) ratio. Means followed by different lowercase (trial 1) and uppercase (trial 2) letters above the bar represent significant differences (n ₌ 10, <span class="html-italic">p</span> ≤ 0.05, one-way ANOVA with post hoc Fisher’s test with an α ₌ 0.05).</p> Full article ">Figure 7
<p>The effect of the treatments on the root gall diameter to the root diameter (RGD/RD) ratio. Means followed by different lowercase (trial 1, representing the gray color) and uppercase (trial 2, representing the black color) letters above the bar represent significant differences (n = 10, <span class="html-italic">p</span> ≤ 0.05, one-way ANOVA with post hoc Fisher’s test with an α = 0.05).</p> Full article ">Figure 8
<p><span class="html-italic">Agrobacterium tumefaciens</span> DNA quantification in the roots of rose. The letters above the bar represent significant differences (n = 10, <span class="html-italic">p</span> ≤ 0.05, one-way ANOVA with post hoc Fisher’s test with an α ₌ 0.05).</p> Full article ">
18 pages, 9708 KiB  
Article
S. mutans Antisense vicK RNA Over-Expression Plus Antibacterial Dimethylaminohexadecyl Methacrylate Suppresses Oral Biofilms and Protects Enamel Hardness in Extracted Human Teeth
by Shuang Yu, Mengmeng Xu, Zheng Wang, Yang Deng, Hockin H. K. Xu, Michael D. Weir, Negar Homayounfar, Guadalupe Garcia Fay, Hong Chen and Deqin Yang
Pathogens 2024, 13(8), 707; https://doi.org/10.3390/pathogens13080707 - 21 Aug 2024
Viewed by 412
Abstract
Streptococcus mutans (S. mutans) antisense vicK RNA (ASvicK) is a non-coding RNA that regulates cariogenic virulence and metabolic activity. Dimethylaminohexadecyl methacrylate (DMAHDM), a quaternary ammonium methacrylate used in dental materials, has strong antibacterial activity. This study examined the effects [...] Read more.
Streptococcus mutans (S. mutans) antisense vicK RNA (ASvicK) is a non-coding RNA that regulates cariogenic virulence and metabolic activity. Dimethylaminohexadecyl methacrylate (DMAHDM), a quaternary ammonium methacrylate used in dental materials, has strong antibacterial activity. This study examined the effects of S. mutans ASvicK on DMAHDM susceptibility and their combined impact on inhibiting S. mutans biofilm formation and protecting enamel hardness. The parent S. mutans UA159 and ASvicK overexpressing S. mutans (ASvicK) were tested. The minimum inhibitory concentration (MIC) and minimum bactericidal concentrations for planktonic bacteria (MBC-P) and biofilms (MBC-B) were measured. As the ASvicK MBC-B was 175 μg/mL, live/dead staining, metabolic activity (MTT), colony-forming units (CFUs), biofilm biomass, polysaccharide, and lactic acid production were investigated at 175 μg/mL and 87.5 μg/mL. The MIC, MBC-P, and MBC-B values for DMAHDM for the ASvicK strain were half those of the UA159 strain. In addition, combining S. mutans ASvicK with DMAHDM resulted in a significant 4-log CFU reduction (p < 0.05), with notable decreases in polysaccharide levels and lactic acid production. In the in vitro cariogenic model, the combination achieved the highest enamel hardness at 67.1% of sound enamel, while UA159 without DMAHDM had the lowest at 16.4% (p < 0.05). Thus, S. mutans ASvicK enhanced DMAHDM susceptibility, and their combination effectively inhibited biofilm formation and minimized enamel demineralization. The S. mutans ASvicK + DMAHDM combination shows great potential for anti-caries dental applications. Full article
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Graphical abstract

Graphical abstract
Full article ">Figure 1
<p>Schematic diagram illustrating the experimental design process for suppressing tooth enamel demineralization in vitro.</p> Full article ">Figure 2
<p>The chemical structure of Dimethylaminohexadecyl methacrylate (DMAHDM) and the drug susceptibility of UA159 and antisense <span class="html-italic">vicK</span> RNA (AS<span class="html-italic">vicK</span>) strains are presented. (<b>A</b>) Hydrogen-1 nuclear magnetic resonance (<sup>1</sup>H-NMR) spectra; (<b>B</b>) Fourier-transform infrared spectroscopy (FTIR) spectra; (<b>C</b>) quantitative real-time PCR (qRT-PCR) verification (mean ± SD; <span class="html-italic">n</span> = 3); (<b>D</b>–<b>F</b>) minimum inhibitory concentration (MIC), minimum bactericidal concentration of planktonic bacteria (MBC-P), and minimum bactericidal concentration of biofilms (MBC-B) (mean ± SD; <span class="html-italic">n</span> = 3); Growth curves of (<b>G</b>) the UA159 and (<b>H</b>) AS<span class="html-italic">vicK</span> strains treated with different mass fractions of DMAHDM for 22 h (mean ± SD; <span class="html-italic">n</span> = 3). Different letters represent significantly different values (<span class="html-italic">p</span> &lt; 0.05).</p> Full article ">Figure 3
<p>Representative live/dead staining images of preformed biofilms treatment of UA159 and AS<span class="html-italic">vicK</span> strains: (<b>A</b>) Live/Dead staining images and the mean fluorescence intensities for live and dead bacteria in each layer of the UA159 strain (mean ± SD; <span class="html-italic">n</span> = 3); (<b>B</b>) Live/Dead staining images and the mean fluorescence intensities for live and dead bacteria in each layer of the AS<span class="html-italic">vicK</span> strain (mean ± SD; <span class="html-italic">n</span> = 3); (<b>C</b>) Mean fluorescence intensity of SYTO 9 (mean ± SD; <span class="html-italic">n</span> = 3); (<b>D</b>) Mean fluorescence intensity of PI (mean ± SD; <span class="html-italic">n</span> = 3); (<b>E</b>) SYTO 9/PI Ratio (mean ± SD; <span class="html-italic">n</span> = 3); Different letters represent significantly different values (<span class="html-italic">p</span> &lt; 0.05).</p> Full article ">Figure 4
<p>Representative SEM images, activity, and virulence factors of preformed UA159 and AS<span class="html-italic">vicK</span> biofilms treated with DMAHDM: (<b>A</b>) SEM images, with the yellow arrows pointing to bacteria while the red arrows point to EPS; (<b>B</b>) Crystal violet staining images; (<b>C</b>) Biofilm biomass (mean ± SD; <span class="html-italic">n</span> = 6); (<b>D</b>) MTT metabolic activity (mean ± SD; <span class="html-italic">n</span> = 6); (<b>E</b>) Colony-forming units (CFUs) (mean ± SD; <span class="html-italic">n</span> = 3). (<b>F</b>) Lactic Acid Production/CFU (mean ± SD; <span class="html-italic">n</span> = 3). Different letters represent significantly different values (<span class="html-italic">p</span> &lt; 0.05).</p> Full article ">Figure 4 Cont.
<p>Representative SEM images, activity, and virulence factors of preformed UA159 and AS<span class="html-italic">vicK</span> biofilms treated with DMAHDM: (<b>A</b>) SEM images, with the yellow arrows pointing to bacteria while the red arrows point to EPS; (<b>B</b>) Crystal violet staining images; (<b>C</b>) Biofilm biomass (mean ± SD; <span class="html-italic">n</span> = 6); (<b>D</b>) MTT metabolic activity (mean ± SD; <span class="html-italic">n</span> = 6); (<b>E</b>) Colony-forming units (CFUs) (mean ± SD; <span class="html-italic">n</span> = 3). (<b>F</b>) Lactic Acid Production/CFU (mean ± SD; <span class="html-italic">n</span> = 3). Different letters represent significantly different values (<span class="html-italic">p</span> &lt; 0.05).</p> Full article ">Figure 5
<p>Representative CLSM images of preformed UA159 and AS<span class="html-italic">vicK</span> biofilms treated with DMAHDM. The EPS was labeled with Alexa Fluor 647, and the bacteria were labeled with SYTO 9. (<b>A</b>) CLSM of the UA159 biofilms; (<b>B</b>) CLSM of the AS<span class="html-italic">vicK</span> biofilms; (<b>C</b>) EPS/Microbe volume ratio of UA159 and AS<span class="html-italic">vicK</span> (mean ± SD; <span class="html-italic">n</span> = 3); (<b>D</b>) Biofilm thickness of UA159 and AS<span class="html-italic">vicK</span> (mean ± SD; <span class="html-italic">n</span> = 3). Different letters represent significantly different values (<span class="html-italic">p</span> &lt; 0.05).</p> Full article ">Figure 6
<p>Polysaccharide amounts and gene expression related to EPS metabolism were analyzed. The biofilm was incubated with BHI containing 1% sucrose for 24 h, followed by incubation with BHI containing DMAHDM for an additional 24 h. (<b>A</b>) Production of WIG (mean ± SD; <span class="html-italic">n</span> = 6); (<b>B</b>) Production of WSG (mean ± SD; <span class="html-italic">n</span> = 6); (<b>C</b>–<b>G</b>) Gene expression of <span class="html-italic">vicK</span>, <span class="html-italic">gtfB</span>/<span class="html-italic">C</span>/<span class="html-italic">D</span> and <span class="html-italic">ftf</span> via qRT-PCR (mean ± SD; <span class="html-italic">n</span> = 3). Different letters represent significantly different values (<span class="html-italic">p</span> &lt; 0.05).</p> Full article ">Figure 7
<p>Hardness of human tooth enamel at the surface after a 28-day acid attack by preformed <span class="html-italic">S. mutans</span> biofilms. The biofilms were treated with 87.5 and 175 μg/mL DMAHDM, respectively. The hardness of sound enamel and demineralized enamel was also measured as comparative controls. The hardness test was conducted at the center of the enamel slab. (mean ± SD, <span class="html-italic">n</span> = 6). Different letters represent significantly different values (<span class="html-italic">p</span> &lt; 0.05).</p> Full article ">
16 pages, 486 KiB  
Review
Advancement in the Antigenic Epitopes and Vaccine Adjuvants of African Swine Fever Virus
by Qiong Wu, Chang Li, Bo Zhu, Jiajia Zhu, Keli Yang, Zewen Liu, Wei Liu, Ting Gao, Fangyan Yuan, Rui Guo, Yongxiang Tian and Danna Zhou
Pathogens 2024, 13(8), 706; https://doi.org/10.3390/pathogens13080706 - 21 Aug 2024
Viewed by 777
Abstract
African swine fever virus (ASFV), a highly virulent double-stranded DNA virus, poses a significant threat to global pig farming, with mortality rates in domestic pigs reaching up to 100%. Originating in Kenya in 1921, ASFV has since proliferated to Western Europe, Latin America, [...] Read more.
African swine fever virus (ASFV), a highly virulent double-stranded DNA virus, poses a significant threat to global pig farming, with mortality rates in domestic pigs reaching up to 100%. Originating in Kenya in 1921, ASFV has since proliferated to Western Europe, Latin America, Eastern Europe, and most recently China in 2018, resulting in substantial global agricultural losses. Antigenic epitopes, recognized by the immune system’s T cells and B cells, are pivotal in antiviral immune responses. The identification and characterization of these antigenic epitopes can offer invaluable insights into the immune response against ASFV and aid in the development of innovative immunotherapeutic strategies. Vaccine adjuvants, substances that amplify the body’s specific immune response to antigens, also play a crucial role. This review provides an overview of the progress in studying T/B-cell epitopes in ASFV proteins and ASFV vaccine adjuvants, highlighting their role in the immune response and potential use in new vaccine development. Full article
(This article belongs to the Special Issue Emergence and Control of African Swine Fever)
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<p>Schematic representation of ASFV structure and location of antigenic epitope-identified proteins in ASFV genomes. (<b>A</b>), Schematic diagram of the ASFV structure. ASFV is composed of an Outer envelope, outer capsid, inner envelope, inner capsid, and nucleoid. (<b>B</b>), Location of antigenic epitope-identified proteins in ASFV genomes.</p> Full article ">
12 pages, 546 KiB  
Article
Japanese Encephalitis Virus Surveillance in U.S. Army Installations in the Republic of Korea from 2021 to 2023
by Paula Lado, Gary P. Crispell, Sung Tae Chong, Myong Sun Kim, Ashley N. Esparza, Eric Zielinski, Akira Iwami, Kelly P. Williams, John J. Eads, Kei Jimbo, Dana N. Mitzel, Lee W. Cohnstaedt, Joshua B. Richardson, Jeffrey R. Kugelman and Craig A. Stoops
Pathogens 2024, 13(8), 705; https://doi.org/10.3390/pathogens13080705 - 20 Aug 2024
Viewed by 527
Abstract
Japanese encephalitis is a disease caused by the Japanese encephalitis virus (JEV) and is a concern for U.S. military personnel stationed in the Republic of Korea (ROK). The recent literature reports a potential shift from GI to GV as the dominant genotype circulating [...] Read more.
Japanese encephalitis is a disease caused by the Japanese encephalitis virus (JEV) and is a concern for U.S. military personnel stationed in the Republic of Korea (ROK). The recent literature reports a potential shift from GI to GV as the dominant genotype circulating in east Asia. In the ROK, GV has been reported in a few Culex spp., but not in the main JEV vector, Cx. tritaeniorhynchus. The goal of this surveillance was to shed light on the current knowledge of the epidemiology of JEV in the ROK by analyzing mosquito collection data from three consecutive years, 2021–2023, and molecularly detecting and genotyping JEV in all Culex spp. collected in several military locations across the ROK. In this study, we detected only JEV GI in Cx. tritaeniorhynchus in 2021 samples. In contrast, all 2022 and 2023 positive samples were GV and detected in Cx. bitaeniorhynchus, Cx. orientalis, and Cx. pipiens. Results support a shift in JEV genotype in the ROK and suggest that for GV, Culex spp. other than Cx. tritaeniorhynchus may be playing an important role. Full article
(This article belongs to the Special Issue The Future of Vector-Borne Diseases in a Changing World)
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<p>Map showing locations mosquito collection sites. Locations where positive pools where detected are shown in light blue circles, whereas locations where no positive pools were detected are shown in dark blue. For locations where positive pools were detected, the year and genotype are indicated by letters (A: 2021; B: 2022; C: 2023) and colors (yellow: JEV genotype I; green: JEV genotype V).</p> Full article ">
11 pages, 2192 KiB  
Article
Seasonal Patterns of Common Respiratory Viral Infections in Immunocompetent and Immunosuppressed Patients
by Fotis Theodoropoulos, Anika Hüsing, Ulf Dittmer, Karl-Heinz Jöckel, Christian Taube and Olympia E. Anastasiou
Pathogens 2024, 13(8), 704; https://doi.org/10.3390/pathogens13080704 - 20 Aug 2024
Viewed by 446
Abstract
Introduction: Several respiratory viruses have been shown to have seasonal patterns. The aim of our study was to evaluate and compare these patterns in immunocompetent and immunosuppressed patients for five different respiratory viruses. Methods: We performed a retrospective analysis of results for 13,591 [...] Read more.
Introduction: Several respiratory viruses have been shown to have seasonal patterns. The aim of our study was to evaluate and compare these patterns in immunocompetent and immunosuppressed patients for five different respiratory viruses. Methods: We performed a retrospective analysis of results for 13,591 respiratory tract samples for human metapneumovirus (HMPV), influenza virus, parainfluenza virus (PIV) and respiratory syncytial virus (RSV) in immunocompetent and immunosuppressed patients. A seasonal pattern was aligned to the data of immunocompetent patients through a logistic regression model of positive and negative test results. Results: A narrow seasonal pattern (January to March) was documented for HMPV. Most RSV infections were detected in the winter and early spring months, from December to March, but occasional cases of RSV could be found throughout the year. The peak season for PIV-3 was during the summer months, and that for PIV-4 was mostly in autumn. A narrow seasonal pattern emerged for influenza virus as most infections were detected in the winter, in January and February. The seasonal patterns of HMPV, RSV, PIV, and influenza virus were similar for both immunocompetent and immunocompromised patients. Conclusions: We found no difference in the seasonality of HMPV, RSV, PIV, and influenza virus infections between immunosuppressed and immunocompetent hosts. Full article
(This article belongs to the Special Issue Epidemiology and Clinical Management of Respiratory Viral Diseases, from Children to Adults)
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<p>HMPV incidence rates: seasonal curve estimated for immunocompetent patients (<b>A</b>) and applied to immunosuppressed patients (<b>B</b>).</p> Full article ">Figure 2
<p>RSV incidence rates: seasonal curve estimated in immunocompetent patients (<b>A</b>) and applied to immunosuppressed patients (<b>B</b>).</p> Full article ">Figure 3
<p>Parainfluenza virus (PIV) 3 incidence rates: seasonal curve estimated in immunocompetent patients (<b>A</b>) and applied to immunosuppressed patients (<b>B</b>).</p> Full article ">Figure 4
<p>Parainfluenza virus (PIV) 4 incidence rates: seasonal curve estimated in immunocompetent patients (<b>A</b>) and applied to immunosuppressed patients (<b>B</b>).</p> Full article ">Figure 5
<p>Influenza virus type A incidence rates: seasonal curve estimated in immunocompetent patients (<b>A</b>) and applied to immunosuppressed patients (<b>B</b>).</p> Full article ">Figure 6
<p>Influenza virus type B incidence rates: seasonal curve estimated in immunocompetent patients (<b>A</b>) and applied to immunosuppressed patients (<b>B</b>).</p> Full article ">Figure 7
<p>Comparing effects of seasonal patterns as optimized among immunocompetent patients in immunosuppressed patients (shaded). The seasonal calendarial pattern was optimized for logistic regression analysis to beta-coefficient = 1, corresponding to OR = exp(1) = 2.72 (reference line). HMPV: human metapneumovirus; RSV: respiratory syncytial virus; PIV: parainfluenza virus; OR: odds ratio; CI: confidence interval.</p> Full article ">
16 pages, 708 KiB  
Review
Geohelminths: Use in the Treatment of Selected Human Diseases
by Magdalena Szuba, Weronika Stachera, Adrianna Piwko, Marianna Misiak, Renata Rutkevich, Marcin Sota, Lana Atrushi, Leyla Bennacer, Deborah Nzekea, Yen Ching Wu, Arya Taesung Kim, Subin Yu, Nash Ribeiro and Monika Dybicz
Pathogens 2024, 13(8), 703; https://doi.org/10.3390/pathogens13080703 - 20 Aug 2024
Viewed by 469
Abstract
Research on the therapeutic use of parasites has been ongoing since the development of the “hygiene hypothesis”. Parasites can stimulate the Th2-dependent response and suppress the Th1-dependent response, which is intensified in many diseases, especially allergic and autoinflammatory ones. In this review, we [...] Read more.
Research on the therapeutic use of parasites has been ongoing since the development of the “hygiene hypothesis”. Parasites can stimulate the Th2-dependent response and suppress the Th1-dependent response, which is intensified in many diseases, especially allergic and autoinflammatory ones. In this review, we present the types of parasites used in helminth therapy and the range of diseases in which they may be useful. We also present the results of clinical trials conducted so far, which confirm the safety of such therapy and provide promising outcomes. Full article
(This article belongs to the Special Issue Immune Response of the Host and Vaccine Development—2nd Edition)
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<p>The life cycle of <span class="html-italic">T. suis.</span> 1. Fertilized adult worm lays unembryonated eggs, which are excreted in the faeces. 2. Unembryonated egg developes in soil. 3. Unembryonated egg becomes embryonated in warm and moist condition. Man acquires infection by ingestion of contaminated soil, food and water. Pigs are the natural host for <span class="html-italic">T. suis</span>. 4. Larva hatches through the pole of the egg in the small intestine. 5. Larva undergoes moults to the adult worm in the mucosal layers. The most of adult worms are located in the large intestine. There are suggestions that most <span class="html-italic">T. suis</span> larvae after hatching in the human gastrointestinal tract remain immature and live there for several weeks.</p> Full article ">Figure 2
<p>The life cycle of hookworm. 1. Fertilized adult worm lays unembryonated eggs, which are excreted in the faeces. 2. Embryonated egg is developed in moist, sandy and warm soil. 3. Rhabditiform larva hatches out from the egg. 4. Rhabditiform larva develops to filariform larva. 5. Humans become infected by penetration of skin (bare foot in dampen soil) by filariform larva. The larva is rarely transmitted via oral, transplacental or transmammary routes. 6. Larva migrates through the bloodstream to the lungs. In the lungs, the larva moves up the respiratory tract, is swallowed, and reaches the small intestine where the larva matures into adult hookworm. The adult hookworm attaches to the intestinal mucosa by their teeth in buccal capsule.</p> Full article ">
23 pages, 3703 KiB  
Review
Interplay between Bile Acids and Intestinal Microbiota: Regulatory Mechanisms and Therapeutic Potential for Infections
by Wenweiran Li, Hui Chen and Jianguo Tang
Pathogens 2024, 13(8), 702; https://doi.org/10.3390/pathogens13080702 - 20 Aug 2024
Viewed by 878
Abstract
Bile acids (BAs) play a crucial role in the human body’s defense against infections caused by bacteria, fungi, and viruses. BAs counteract infections not only through interactions with intestinal bacteria exhibiting bile salt hydrolase (BSH) activity but they also directly combat infections. Building [...] Read more.
Bile acids (BAs) play a crucial role in the human body’s defense against infections caused by bacteria, fungi, and viruses. BAs counteract infections not only through interactions with intestinal bacteria exhibiting bile salt hydrolase (BSH) activity but they also directly combat infections. Building upon our research group’s previous discoveries highlighting the role of BAs in combating infections, we have initiated an in-depth investigation into the interactions between BAs and intestinal microbiota. Leveraging the existing literature, we offer a comprehensive analysis of the relationships between BAs and 16 key microbiota. This investigation encompasses bacteria (e.g., Clostridioides difficile (C. difficile), Staphylococcus aureus (S. aureus), Escherichia coli, Enterococcus, Pseudomonas aeruginosa, Mycobacterium tuberculosis (M. tuberculosis), Bacteroides, Clostridium scindens (C. scindens), Streptococcus thermophilus, Clostridium butyricum (C. butyricum), and lactic acid bacteria), fungi (e.g., Candida albicans (C. albicans) and Saccharomyces boulardii), and viruses (e.g., coronavirus SARS-CoV-2, influenza virus, and norovirus). Our research found that Bacteroides, C. scindens, Streptococcus thermophilus, Saccharomyces boulardii, C. butyricum, and lactic acid bacteria can regulate the metabolism and function of BSHs and 7α-dehydroxylase. BSHs and 7α-dehydroxylase play crucial roles in the conversion of primary bile acid (PBA) to secondary bile acid (SBA). It is important to note that PBAs generally promote infections, while SBAs often exhibit distinct anti-infection roles. In the antimicrobial action of BAs, SBAs demonstrate antagonistic properties against a wide range of microbiota, with the exception of norovirus. Given the intricate interplay between BAs and intestinal microbiota, and their regulatory effects on infections, we assert that BAs hold significant potential as a novel approach for preventing and treating microbial infections. Full article
(This article belongs to the Section Immunological Responses and Immune Defense Mechanisms)
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<p>The mechanism of BAs regulating infection. BAs (<b>A</b>) regulate the abundance of intestinal microbiota. PBAs (<b>B</b>) promote pathogen proliferation and (<b>C</b>) increase intestinal epithelial permeability. SBAs (<b>D</b>) exhibit anti-inflammatory effects; (<b>E</b>) inhibit pathogen proliferation; and (<b>F</b>) strengthen intestinal barrier function. BA: bile acid; PBA: primary bile acid; SBA: secondary bile acid.</p> Full article ">Figure 2
<p>Interactions between BAs and <span class="html-italic">Candida albicans</span>. PBAs (<b>A</b>) reduce the tight junction proteins in the intestine; (<b>B</b>) inhibit the production of immune active substances angiogenin-4 and CX3CR1; (<b>C</b>) and increase the abundance of enterohemorrhagic <span class="html-italic">Escherichia coli</span>. SBAs (<b>D</b>) inhibit the transition of <span class="html-italic">C. albicans</span> from yeast to virulent hyphal form and from planktonic to biofilm phase and (<b>E</b>) direct antimicrobial activity against <span class="html-italic">C. albicans</span>. <span class="html-italic">C. albicans</span> (<b>F</b>) reduces the abundance of intestinal bacteria exhibiting BSH activity. PBA: primary bile acid; SBA: secondary bile acid; BSH: bile salt hydrolase; <span class="html-italic">C. albicans</span>: <span class="html-italic">Candida albicans</span>.</p> Full article ">Figure 3
<p>Interactions between BAs and <span class="html-italic">Clostridioides difficile</span>. PBAs (<b>A</b>) promote the spore germination of <span class="html-italic">C. difficile</span>. SBAs (<b>B</b>) bind to FXR and TGR5 receptors, activating NF-κB and other signaling pathways, enhancing innate immunity, and inhibiting the growth of <span class="html-italic">C. difficile</span>, and (<b>C</b>) interact with the C-terminus of toxin TcdB directly, inducing toxin structural changes, and preventing toxin binding with host cells. <span class="html-italic">C. difficile</span> (<b>D</b>) promotes the release of <span class="html-italic">C. difficile</span> toxins TcdA and TcdB and (<b>E</b>) induces intestinal inflammation. PBA: primary bile acid; SBA: secondary bile acid; FXR: Farnesoid X Receptor; TGR5: Takeda G Protein-Coupled Receptor 5; <span class="html-italic">C. difficile</span>: <span class="html-italic">Clostridioides difficile</span>.</p> Full article ">Figure 4
<p>Interactions between BAs and <span class="html-italic">Enterococci</span> and other pathogenic bacteria. PBAs (<b>A</b>) regulate the synthesis of virulence-related metabolites, such as the iron chelator pyochelin, thereby affecting <span class="html-italic">Pseudomonas aeruginosa</span>’s toxicity, and inhibit its biofilm formation. SBAs (<b>B</b>) inhibit the expression of ribosomal protein genes, suppressing the growth of <span class="html-italic">E. faecalis</span>; (<b>C</b>) maintain VRE in a diplococcal state and inhibit the morphological transformation of VRE; (<b>D</b>) inhibit the formation of <span class="html-italic">VRE</span> biofilms; (<b>E</b>) optimize the structure of the intestinal microbiota; (<b>F</b>) increase TGR5 transcription, thereby enhancing innate immunity, and strengthen the intestinal barrier; and (<b>G</b>) disrupt the cell wall of lipid-rich <span class="html-italic">M. tuberculosis</span>. ESBL-EAEC (<b>H</b>) reduces the abundance of intestinal bacteria exhibiting BSH activity. PBA: primary bile acid; SBA: secondary bile acid; VRE: <span class="html-italic">vancomycin-resistant enterococci.</span> TGR5: Takeda G Protein-Coupled Receptor 5.</p> Full article ">Figure 5
<p>Interactions between BAs and <span class="html-italic">Bacteroidetes</span>. (<b>A</b>) <span class="html-italic">Bacteroidetes</span> exhibit BSH activity, facilitate SBA production, and alleviate colitis; (<b>B</b>) <span class="html-italic">Bacteroides</span> with high BSH gene expression will promote the massive production of SBA, which can induce colorectal cancer; (<b>C</b>) BDX-01 enhances intestinal health by modulating BA metabolism and the FXR-NLRP3 inflammasome signaling pathway, thus mitigating experimental colitis. PBA: primary bile acid; SBA: secondary bile acid; BSH: bile salt hydrolase; FXR: Farnesoid X Receptor.</p> Full article ">Figure 6
<p>Interactions between BAs and <span class="html-italic">Clostridium scindens</span>. <span class="html-italic">C. scindens</span> (<b>A</b>) exhibits BSH and 7α-dehydroxylase activity, facilitates SBA production, and inhibits <span class="html-italic">C. difficile</span> infection; (<b>B</b>) inhibitd the toxin production of <span class="html-italic">C. difficile</span>; and (<b>C</b>) reduces <span class="html-italic">C. difficile</span> overall count. PBA: primary bile acid; SBA: secondary bile acid; BSH: bile salt hydrolase; <span class="html-italic">C. difficile</span>: <span class="html-italic">Clostridioides difficile</span>; <span class="html-italic">C. scindens</span>: <span class="html-italic">Clostridium scindens</span>.</p> Full article ">Figure 7
<p>Interactions between BAs and <span class="html-italic">Clostridium butyricum</span>. <span class="html-italic">C. butyricum</span> (<b>A</b>) modulates the ratio of PBAs to SBAs and (<b>B</b>) promotes the production of CBA. CBA improves intrauterine growth restriction and reduce liver inflammation by activating LXRα and FXR; (<b>C</b>) enhances the production of butyric acid, which ameliorates chronic pancreatitis and strengthens the tight junctions of intestinal epithelial cells, thereby reducing intestinal barrier damage and restoring the intestinal immune microenvironment; (<b>D</b>) inhibits lipid synthesis; and (<b>E</b>) coordinates SBA regulation to activate FXR and inhibit TGR5, thereby regulating blood sugar and reducing obesity. PBA: primary bile acid; SBA: secondary bile acid; BSH: bile salt hydrolase; LXRα: liver X receptor alpha; FXR: Farnesoid X Receptor; CBA: conjugated bile acid; <span class="html-italic">C. butyricum</span>: <span class="html-italic">Clostridium butyricum</span>.</p> Full article ">Figure 8
<p>Interactions between UDCA and Coronavirus SARS-CoV-2. UDCA (<b>A</b>) directly damages the virus structure, inhibiting its replication; (<b>B</b>) reduces the affinity between the receptor-binding domain of coronavirus SARS-CoV-2 and the host ACE2; (<b>C</b>) inhibits FXR gene expression, thereby suppressing ACE2 expression; (<b>D</b>) increases the abundance of <span class="html-italic">Collinsella</span> and promotes the synthesis of 7β-Hydroxysteroid dehydrogenase, ameliorating acute respiratory distress syndrome in COVID-19; and (<b>E</b>) possesses anti-inflammatory, antioxidative, immunomodulatory, and anti-apoptotic properties. UDCA: ursodeoxycholic acid; SARS-CoV-2: Severe Acute Respiratory Syndrome Coronavirus 2; FXR: Farnesoid X Receptor; ACE2: angiotensin-converting enzyme 2; SBA: secondary bile acid.</p> Full article ">Figure 9
<p>Interactions between BAs and Other Viruses. (<b>A</b>) STH manifests antiviral activity against IVA infections through the modulation of signaling pathways, including TLR4/NF-κB; (<b>B</b>) CDCA demonstrates the capacity to attenuate IAV infections by inhibiting the nuclear export of vRNPs; (<b>C</b>) CDCA can reduce virus-induced lipid synthesis, inhibiting the replication of rotavirus; (<b>D</b>) CDCA activates FXR and TGR5 receptors to counteract HBV infection; (<b>E</b>) GCDCA enhances the virulence of norovirus through a mechanism that is not yet clarified. STH: sodium taurocholate; TLR4: Toll-like receptor 4; CDCA: chenodeoxycholic acid; vRNPs: viral ribonucleoproteins; IAV: influenza A virus; GCDCA: glycine deoxycholic acid; FXR: Farnesoid X Receptor; TGR5: Takeda G Protein-Coupled Receptor 5; HBV: hepatitis B virus.</p> Full article ">
17 pages, 3908 KiB  
Article
A New Ex Vivo Model Based on Mouse Retinal Explants for the Study of Ocular Toxoplasmosis
by Veronica Rodriguez Fernandez, Rosario Amato, Simona Piaggi, Barbara Pinto, Giovanni Casini and Fabrizio Bruschi
Pathogens 2024, 13(8), 701; https://doi.org/10.3390/pathogens13080701 - 19 Aug 2024
Viewed by 451
Abstract
Ocular toxoplasmosis is the most prevalent clinical manifestation of T. gondii infection, which causes irreversible retinal damage. Different experimental models have been developed to study this pathology. In the present study, a new, ex vivo model is proposed to contribute to the elucidation [...] Read more.
Ocular toxoplasmosis is the most prevalent clinical manifestation of T. gondii infection, which causes irreversible retinal damage. Different experimental models have been developed to study this pathology. In the present study, a new, ex vivo model is proposed to contribute to the elucidation of disease mechanisms and to possible therapeutic solutions. Ex-vivo retinal explants, prepared from mouse retinas following established protocols, were incubated with T. gondii tachyzoites maintained in Vero cells. At different times, starting at 12 h up to 10 days of incubation, the explants were analyzed with immunofluorescence and Western blot to investigate their responses to parasite infection. T. gondii invasion of the retinal thickness was evident after 3 days in culture, where parasites could be detected around retinal cell nuclei. This was paralleled by putative cyst formation and microglial activation. At the same time, an evident increase in inflammatory and oxidative stress markers was detected in infected explants compared to controls. Cell death also appeared to occur in retinal explants after 3 days of T. gondii infection, and it was characterized by increased necroptotic but not apoptotic markers. The proposed model recapitulates the main characteristics of T. gondii retinal infection within 3 days of incubation and, therefore, allows for studying the very early events of the process. In addition, it requires only a limited number of animals and offers easy manipulation and accessibility for setting up different experimental conditions and assessing the effects of putative drugs for therapy. Full article
(This article belongs to the Section Parasitic Pathogens)
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<p>Procedure for <span class="html-italic">T. gondii</span> infection of cultured retinal explants. <span class="html-italic">T. gondii</span> (TG) from Vero cell cultures were isolated and counted (<b>A</b>). Aliquots of 2,000 or 20,000 TG were suspended in 500 μL of culture medium (<b>B</b>) and transferred onto the membrane of a culture insert. Due to the small pore size of the insert membrane (0.4 µm diameter), the medium was drained while TG remained on the membrane (<b>C</b>). The TG-containing insert was then moved into a culture well (<b>D</b>) containing 1 mL of culture medium. Retinal explants were prepared from retinas of 3–5-week-old C57BL/6J mice (<b>E</b>). Each retina was divided into four fragments (<b>F</b>), and the fragments (retinal explants) were positioned ganglion cells up onto the membrane of the culture insert (<b>G</b>). A total of six explants were laid in each insert (although only one is shown in the figure). See the text for a more detailed description.</p> Full article ">Figure 2
<p>Representative DAPI-stained sections from control retinal explants (<b>A</b>) and from explants after 1 day (<b>B</b>), 3 days (<b>C</b>), 7 days (<b>D</b>), and 10 days (<b>E</b>) of incubation in the presence of <span class="html-italic">T. gondii</span> showing only minor alterations of retinal layer organization throughout the culture period. Scale bar, 50 μm. (<b>F</b>–<b>J</b>): Representative low-power photomicrographs of sections immunolabeled with an antibody directed to <span class="html-italic">T. gondii</span> and obtained from control retinal explants (<b>F</b>) and from explants after 1 day (<b>G</b>), 3 days (<b>H</b>), 7 days (<b>I</b>), and 10 days (<b>J</b>) of incubation in the presence of <span class="html-italic">T. gondii</span>. Scale bar: 20 μm. Abbreviations: GCL, ganglion cell layer; INL, inner nuclear layer; IPL, inner plexiform layer; ONL, outer nuclear layer; OPL, outer plexiform layer.</p> Full article ">Figure 3
<p>Representative photomicrographs of sections from retinal explants immunolabeled with an antibody directed to <span class="html-italic">T. gondii</span>. (<b>A</b>–<b>C</b>): Immunolabeled sections from control retinal explants ((<b>A</b>), with DAPI counterstain) and from explants after 12 h (<b>B</b>) and 1 day (<b>C</b>) of incubation in the presence of <span class="html-italic">T. gondii</span>. The arrows point to <span class="html-italic">T. gondii</span> immunofluorescence localized superficially to both the GCL and the ONL sides of the explant. Scale bar, 50 μm. (<b>D</b>,<b>E</b>): Higher-power photomicrographs of retinal sections from retinal explants after 3 days and 7 days, respectively, of incubation with <span class="html-italic">T. gondii</span> ((<b>E</b>) with DAPI counterstain). Scale bars: (<b>D</b>) 50 μm (inset, 10 μm); (<b>E</b>) 10 μm. See <a href="#pathogens-13-00701-f002" class="html-fig">Figure 2</a> for abbreviations.</p> Full article ">Figure 4
<p>Representative photomicrographs of sections from retinal explants immunolabeled with an antibody directed to <span class="html-italic">T. gondii</span> (and counterstained with DAPI) showing the presence of immunolabeled putative cysts localized to different retinal layers after 3 days (<b>A</b>–<b>C</b>) and 7 days (<b>D</b>,<b>E</b>) of incubation with <span class="html-italic">T. gondii</span>. Scale bar: 50 μm. POS, photoreceptor outer layer. See <a href="#pathogens-13-00701-f002" class="html-fig">Figure 2</a> for other abbreviations.</p> Full article ">Figure 5
<p>Representative photomicrographs of sections double-labeled with antibodies directed to <span class="html-italic">T. gondii</span> (TG, green) and ionized calcium-binding adapter molecule 1 (Iba1, red) from control retinal explants (<b>A</b>–<b>D</b>) and from explants after 1 day (<b>E</b>–<b>H</b>) and 3 days (<b>I</b>–<b>L</b>) of incubation in the presence of <span class="html-italic">T. gondii</span>. The sections were counterstained with DAPI. Scale bar, 50 μm. See <a href="#pathogens-13-00701-f002" class="html-fig">Figure 2</a> for abbreviations.</p> Full article ">Figure 6
<p>Western blot analysis showing representative immunoreactive bands and quantitative densitometric analysis of pNF-kB p65/NF-kB p65 ratio (<b>A</b>) and of IL-6 protein levels (<b>B</b>) in control retinal explants and from explants after 1 day and 3 days of incubation in the presence of <span class="html-italic">T. gondii</span>. ** <span class="html-italic">p</span> &lt; 0.01; *** <span class="html-italic">p</span> &lt; 0.001.</p> Full article ">Figure 7
<p>Representative photomicrographs of sections immunolabeled with an antibody directed to inducible nitric oxide synthase (iNOS, (<b>A</b>,<b>B</b>)) or endothelial NOS (eNOS, (<b>C</b>,<b>D</b>)) from control retinal explants (<b>A</b>,<b>C</b>) and from explants after 3 days of incubation in the presence of <span class="html-italic">T. gondii</span> (<b>B</b>,<b>D</b>). The sections were counterstained with DAPI. The arrows in (<b>C</b>,<b>D</b>) point to eNOS-immunolabeled blood capillaries. Scale bar, 50 μm (inset, 20 μm). See <a href="#pathogens-13-00701-f004" class="html-fig">Figure 4</a> for abbreviations.</p> Full article ">Figure 8
<p>Representative photomicrographs of sections immunolabeled with an antibody directed to matrix metalloproteinase-2 (MMP-2, (<b>A</b>,<b>B</b>)) or 4-hydroxynonenal (4-HNE, (<b>C</b>,<b>D</b>)) from control retinal explants (<b>A</b>,<b>C</b>) and from explants after 3 days of incubation in the presence of <span class="html-italic">T. gondii</span> (<b>B</b>,<b>D</b>). The sections were counterstained with DAPI. Scale bar, 50 μm. See <a href="#pathogens-13-00701-f004" class="html-fig">Figure 4</a> for abbreviations.</p> Full article ">Figure 9
<p>Representative photomicrographs of sections immunolabeled with an antibody directed to receptor-interacting serine/threonine kinase 1 (RIPK1, (<b>A</b>,<b>B</b>)), to RIPK3 (<b>C</b>,<b>D</b>) or to active caspase-3 (Casp-3) from control retinal explants (<b>A</b>,<b>C</b>,<b>E</b>) and from explants after 3 days of incubation in the presence of <span class="html-italic">T. gondii</span> (<b>B</b>,<b>D</b>,<b>F</b>). The sections were counterstained with DAPI. Scale bar, 50 μm. See <a href="#pathogens-13-00701-f004" class="html-fig">Figure 4</a> for abbreviations.</p> Full article ">
18 pages, 7582 KiB  
Article
Phylogenetics and Mobilization of Genomic Traits of Cephalosporin-Resistant Escherichia coli Originated from Retail Meat
by Ewelina Iwan, Magdalena Zając, Arkadiusz Bomba, Małgorzata Olejnik, Magdalena Skarżyńska, Bernard Wasiński, Kinga Wieczorek, Katarzyna Tłuścik and Dariusz Wasyl
Pathogens 2024, 13(8), 700; https://doi.org/10.3390/pathogens13080700 - 19 Aug 2024
Viewed by 485
Abstract
Contaminations with cephalosporin-resistant Escherichia coli across the food chain may pose a significant threat to public health because those antimicrobials are critically important in human medicine. The impact of the presented data is especially significant concerning Poland’s role as one of the leading [...] Read more.
Contaminations with cephalosporin-resistant Escherichia coli across the food chain may pose a significant threat to public health because those antimicrobials are critically important in human medicine. The impact of the presented data is especially significant concerning Poland’s role as one of the leading food producers in the EU. This work aimed to characterize the genomic contents of cephalosporin-resistant Escherichia coli (n = 36) isolated from retail meat to expand the official AMR monitoring reported by EFSA. The ESBL mechanism was predominant (via blaCTX-M-1 and blaSHV-12), with the AmpC-type represented by the blaCMY-2 variant. The strains harbored multiple resistance genes, mainly conferring resistance to aminoglycosides, sulfonamides, trimethoprim, tetracyclines. In some isolates, virulence factors—including intimin (eae) and its receptor (tir) were detected, indicating significant pathogenic potential. Resistance genes showed a link with IncI1 and IncB/O/K/Z plasmids. Cephalosporinases were particularly linked to ISEc9/ISEc1 (blaCTX-M-1 and blaCMY-2). The association of virulence with mobile elements was less common—mostly with IncF plasmids. The analysis of E. coli isolated from retail meat indicates accumulation of ARGs and their association with various mobile genetic elements, thus increasing the potential for the transmission of resistance across the food chain. Full article
(This article belongs to the Special Issue Virulence and Resistance Mechanisms in Multidrug-Resistant Gram-Negative Bacteria)
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Figure 1
<p>(<b>a</b>) Phylogeny of characterized <span class="html-italic">E. coli</span> from retail meat, based on core genome markers (cgMLST). The presented dataset describes the origin, sequence type, identified antigens, number of detected ARGs from each antibiotic class, and mechanisms of resistance to cephalosporins associated with identified gene variants. (<b>b</b>) Core genome (cgMLST) phylogenetic tree of <span class="html-italic">E. coli</span> strains characterized across this study (n = 36), color-coded in accordance with isolation source, as well as <span class="html-italic">E. coli</span> sequences (n = 42) from Polish meat production chain (beef carcasses), acquired from EnteroBase (color-coded green).</p> Full article ">Figure 1 Cont.
<p>(<b>a</b>) Phylogeny of characterized <span class="html-italic">E. coli</span> from retail meat, based on core genome markers (cgMLST). The presented dataset describes the origin, sequence type, identified antigens, number of detected ARGs from each antibiotic class, and mechanisms of resistance to cephalosporins associated with identified gene variants. (<b>b</b>) Core genome (cgMLST) phylogenetic tree of <span class="html-italic">E. coli</span> strains characterized across this study (n = 36), color-coded in accordance with isolation source, as well as <span class="html-italic">E. coli</span> sequences (n = 42) from Polish meat production chain (beef carcasses), acquired from EnteroBase (color-coded green).</p> Full article ">Figure 2
<p>The matrix summarizes the presence of virulence factors (VFs) in the genomes of <span class="html-italic">E. coli</span>, categorized by their isolation sources: beef, broiler meat, and pork. In the matrix, the presence of each VF is indicated in black. The distribution of VFs across strains is represented by shades of violet, with the total number of detected VFs per strain ranging from a minimum of 12 (lilac) to a maximum of 42 (purple), as indicated in the legend.</p> Full article ">Figure 3
<p>The matrix summarizing the presence of plasmid replicons in <span class="html-italic">E. coli</span> genomes grouped according to isolation sources—beef, broiler meat, and pork. The presence of replicons is indicated in black on the matrix. The distribution of green color represents the total number of detected plasmid replicons per strain, ranging from light green (minimum, n = 1) to dark green (maximum, n = 9), as illustrated in the legend.</p> Full article ">Figure 4
<p>(<b>a</b>,<b>b</b>) Association between antimicrobial resistance genes and MGEs, both plasmid replicons and IS/Tn; (<b>a</b>) ARGs of all antibiotic classes, with the exception of cephalosporins, which are presented in (<b>b</b>). The link between the resistance gene and MGEs was established when both were in direct proximity (up to 3 kb) in genome assembly.</p> Full article ">Figure 5
<p>(<b>a</b>–<b>c</b>) Annotated fragments of <span class="html-italic">E. coli</span> genomes that contain resistance genes linked to MGEs. (<b>a</b>) Sample 170901_0261, harboring IncN replicon with multiple ARGs (<span class="html-italic">aph</span>(6)-Id, <span class="html-italic">aph</span>(3″)-Ib, <span class="html-italic">dfrA1</span>, <span class="html-italic">aph</span>(3″)-Ib, <span class="html-italic">sul2</span>, <span class="html-italic">tet</span>A/R); (<b>b</b>) sample 170901_0259 harboring IncB/O/K/Z replicon with MDR cassette (<span class="html-italic">dfrA1</span>, <span class="html-italic">aadA1</span>, <span class="html-italic">aph</span>(6)-Id, <span class="html-italic">aph</span>(3″)-Ib, <span class="html-italic">qacE</span>, <span class="html-italic">sul1</span>); (<b>c</b>) sample 171110_0340 harboring IncX1 replicon with <span class="html-italic">mcr-1.1</span> gene, aligned with reference sequence of mcr-plasmid MK869757.1 (color-coded green).</p> Full article ">Figure 6
<p>Association between virulence factors and MGEs, both plasmid replicons and IS/tn. The link between VF and MGE was established when both were in direct proximity (up to 3 kb) in the genome assembly.</p> Full article ">Figure 7
<p>Annotated fragment of the strain 171110_0341 genome, harboring virulence factors <span class="html-italic">(iroN</span>, <span class="html-italic">mchF</span>, <span class="html-italic">etsC</span>, <span class="html-italic">ompT</span>, <span class="html-italic">etsC</span>, <span class="html-italic">cvaC</span>, <span class="html-italic">iss</span>, <span class="html-italic">anr</span>, <span class="html-italic">tsh</span>, <span class="html-italic">hlyF</span>) with multiple IS and two plasmid replicons: IncFIB and IncFIC.</p> Full article ">
12 pages, 1253 KiB  
Article
Green Tea Catechin Epigallocatechin Gallate Inhibits Vegetative Cell Outgrowth and Expression of Beta-Lactamase Genes in Penicillin-Resistant Bacillus anthracis Strain PCr
by Akiko Okutani, Shigeru Morikawa and Ken Maeda
Pathogens 2024, 13(8), 699; https://doi.org/10.3390/pathogens13080699 - 19 Aug 2024
Viewed by 441
Abstract
The green tea catechin epigallocatechin gallate (EGCg) has antimicrobial effects on many bacteria. In this study, we investigated the inhibitory effects of EGCg on Bacillus anthracis spores and vegetative cells. The B. anthracis spores were insensitive to EGCg, but the growth of vegetative [...] Read more.
The green tea catechin epigallocatechin gallate (EGCg) has antimicrobial effects on many bacteria. In this study, we investigated the inhibitory effects of EGCg on Bacillus anthracis spores and vegetative cells. The B. anthracis spores were insensitive to EGCg, but the growth of vegetative cells derived from germinated spores was inhibited by EGCg. Moreover, EGCg decreased the minimum inhibitory concentration of penicillin and meropenem for penicillin-resistant B. anthracis. In the penicillin-resistant B. anthracis strain, the transcription levels of the beta-lactamase genes (bla1 and bla2) decreased significantly following the treatment with 50 µg/mL EGCg. These results suggest that the appropriate application of EGCg may effectively control the penicillin-resistant B. anthracis growth and beta-lactamase production. Full article
(This article belongs to the Special Issue Bacillus anthracis and Bacillus cereus: Understanding the Pathogenicity and Host Interactions)
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<p>Schematic overview of experimental design for investigating EGCg effects on <span class="html-italic">B. anthracis</span> of MIC determination, spore germination studies, time-kill assays, and beta-lactamase activity and gene expression analysis.</p> Full article ">Figure 2
<p>(<b>a</b>) Growth curve from spores of penicillin-resistant <span class="html-italic">Bacillus anthracis</span> strain PCr treated without EGCg (no-treatment control) or with 100 μg/mL EGCg. The optical density at 600 nm (OD<sub>600</sub>) was calculated (relative to the initial OD<sub>600</sub>). Significant differences from the no-treatment control are indicated by asterisks: * <span class="html-italic">p</span> &lt; 0.05 and **** <span class="html-italic">p</span> &lt; 0.0001. The graph inset presents the decrease in OD<sub>600</sub> due to spore germination. (<b>b</b>) Growth curve of vegetative cells of penicillin-resistant <span class="html-italic">B. anthracis</span> strain PCr treated with EGCg (25, 50, and 100 μg/mL). Colony-forming unit (CFU)/mL was calculated after 3, 6, 9, 12, and 27 h incubations. Significant differences from the no-treatment control are indicated by asterisks: * <span class="html-italic">p</span> &lt; 0.05 and **** <span class="html-italic">p</span> &lt; 0.0001. (<b>c</b>) Growth curve of vegetative cells of wild-type <span class="html-italic">B. anthracis</span> strain BA103 treated with EGCg (25, 50, and 100 μg/mL). Colony-forming unit (CFU)/mL was calculated after 3, 6, 9, 12, and 27 h incubations. Significant differences from the no-treatment control are indicated by asterisks: * <span class="html-italic">p</span> &lt; 0.05 and **** <span class="html-italic">p</span> &lt; 0.0001.</p> Full article ">Figure 2 Cont.
<p>(<b>a</b>) Growth curve from spores of penicillin-resistant <span class="html-italic">Bacillus anthracis</span> strain PCr treated without EGCg (no-treatment control) or with 100 μg/mL EGCg. The optical density at 600 nm (OD<sub>600</sub>) was calculated (relative to the initial OD<sub>600</sub>). Significant differences from the no-treatment control are indicated by asterisks: * <span class="html-italic">p</span> &lt; 0.05 and **** <span class="html-italic">p</span> &lt; 0.0001. The graph inset presents the decrease in OD<sub>600</sub> due to spore germination. (<b>b</b>) Growth curve of vegetative cells of penicillin-resistant <span class="html-italic">B. anthracis</span> strain PCr treated with EGCg (25, 50, and 100 μg/mL). Colony-forming unit (CFU)/mL was calculated after 3, 6, 9, 12, and 27 h incubations. Significant differences from the no-treatment control are indicated by asterisks: * <span class="html-italic">p</span> &lt; 0.05 and **** <span class="html-italic">p</span> &lt; 0.0001. (<b>c</b>) Growth curve of vegetative cells of wild-type <span class="html-italic">B. anthracis</span> strain BA103 treated with EGCg (25, 50, and 100 μg/mL). Colony-forming unit (CFU)/mL was calculated after 3, 6, 9, 12, and 27 h incubations. Significant differences from the no-treatment control are indicated by asterisks: * <span class="html-italic">p</span> &lt; 0.05 and **** <span class="html-italic">p</span> &lt; 0.0001.</p> Full article ">Figure 3
<p>Production of β-lactamase in penicillin-resistant and wild-type <span class="html-italic">Bacillus anthracis</span>. Overnight cultures of penicillin-resistant <span class="html-italic">B. anthracis</span> (PCr) (<b>a</b>) and wild-type <span class="html-italic">B. anthracis</span> (BA103) (<b>b</b>) in MH broth supplemented with EGCg (0, 10, 50, 100, and 500 μg/mL) were added to Cefinase discs. The production of β-lactamase was indicated by a change in disc color (yellow to red). The intensity of the color change reflected the extent of β-lactamase production.</p> Full article ">Figure 4
<p>Analysis of β-lactamase gene (<span class="html-italic">bla1</span> and <span class="html-italic">bla2</span>) expression in <span class="html-italic">Bacillus anthracis</span> PCr grown in MH broth supplemented with EGCg (25 and 50 µg/mL) and in <span class="html-italic">B. anthracis</span> BA103 with EGCg 50 µg/mL. The <span class="html-italic">bla1</span> (<b>a</b>) and <span class="html-italic">bla2</span> (<b>b</b>) mRNA levels after 1.5, 3, and 6 h incubations were determined by qRT-PCR and normalized against <span class="html-italic">gapA</span> mRNA levels. The mean and standard deviation were calculated from two independent experiments. Significant differences between EGCg treatments and the no-treatment control are indicated.</p> Full article ">
21 pages, 2832 KiB  
Article
The Antibacterial Efficacy of Far-UVC Light: A Combined-Method Study Exploring the Effects of Experimental and Bacterial Variables on Dose–Response
by David T. Griffin, Terence Gourlay and Michelle Maclean
Pathogens 2024, 13(8), 698; https://doi.org/10.3390/pathogens13080698 - 19 Aug 2024
Viewed by 576
Abstract
Far-ultraviolet C light, with a wavelength of 200–230 nm, has demonstrated broad-spectrum germicidal efficacy. However, due to increased interest in its use as an alternative antimicrobial, further knowledge about its fundamental bactericidal efficacy is required. This study had two objectives. Firstly, it investigated [...] Read more.
Far-ultraviolet C light, with a wavelength of 200–230 nm, has demonstrated broad-spectrum germicidal efficacy. However, due to increased interest in its use as an alternative antimicrobial, further knowledge about its fundamental bactericidal efficacy is required. This study had two objectives. Firstly, it investigated experimentally the Far-UVC dose–response of common bacteria suspended at various cell densities in transparent buffer, ensuring no influence from photosensitive suspending media. Increasing doses of Far-UVC were delivered to Enterococcus faecium, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus in PBS at 101, 102, 103, 105 and 107 CFU·mL−1, with surviving colony-forming units enumerated (n ≥ 3). Secondly, through a systematised literature review, this work sought to explore the impact of genus/species, Gram type, cell form, cell density and irradiance on dose–response. The screening of 483 publications was performed with 25 included in the study. Data for 30 species were collated, analysed and compared with the experimental results. Overall, Gram-positive species showed greater resilience to Far-UVC than Gram-negative; some inter-species and inter-genera differences in resilience were identified; endospores were more resilient than vegetative cells; the results suggested that inactivation efficiency may decrease as cell density increases; and no significant correlation was identified between irradiance and bactericidal dose effect. In conclusion, this study has shown Far-UVC light to be an effective decontamination tool against a vast range of bacterial vegetative cells and endospores. Full article
(This article belongs to the Section Epidemiology of Infectious Diseases)
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<p>Optical profile of the Unilam Kr-Cl excimer lamp. (<b>a</b>) Emission spectrum from the lamp with the power supply set to 180 V, captured using HR4000 spectrometer. Peak emission at 220.97 nm. (<b>b</b>) Irradiance map at 35 cm from Kr-Cl surface over the surface area of a 6-well plate (with the plate outline superimposed on the irradiance map). Irradiance values account for a reduction in transmission caused by a quartz window which covered sample plates during irradiation.</p> Full article ">Figure 2
<p>Flowchart outlining the publication selection process and the number of publications at each stage in the systematised review, based on the inclusion and exclusion criteria.</p> Full article ">Figure 3
<p>Bacterial inactivation of <span class="html-italic">E. coli</span>, <span class="html-italic">E. faecium</span>, <span class="html-italic">P. aeruginosa</span> and <span class="html-italic">S. aureus</span> suspended in PBS in cell densities of (<b>a</b>) 10<sup>1</sup>, (<b>b</b>) 10<sup>2</sup>, (<b>c</b>) 10<sup>3</sup>, (<b>d</b>) 10<sup>5</sup> and (<b>e</b>) 10<sup>7</sup> CFU·mL<sup>−1</sup>, using increasing doses of Far-UVC light and an irradiance of 0.62 mW·cm<sup>−2</sup> (<span class="html-italic">n</span> ≥ 3 ± SD; detection limit ≤20 CFU·mL<sup>−1</sup>); * denotes significant inactivation compared with its respective starting population (paired <span class="html-italic">t</span>-test, <span class="html-italic">p</span> &lt; 0.05). (<b>f</b>) Comparison of the dose required to achieve near complete inactivation (&lt;20 CFU·mL<sup>−1</sup> surviving) for each bacterial species for each cell density.</p> Full article ">Figure 4
<p>Bacterial cell density (Log<sub>10</sub> CFU·mL<sup>−1</sup>) versus measured Far-UVC 1-Log<sub>10</sub> ID for (<b>a</b>) <span class="html-italic">E. coli</span>, (<b>b</b>) <span class="html-italic">E. faecium</span>, (<b>c</b>) <span class="html-italic">P. aeruginosa</span> and (<b>d</b>) <span class="html-italic">S. aureus</span>. 1-Log<sub>10</sub> ID calculated by dividing the dose (mJ·cm<sup>−2</sup>) at which the greatest statistically significant inactivation was achieved prior to tailing by the corresponding mean inactivation (Log<sub>10</sub> CFU·mL<sup>−1</sup>) (based on the inactivation kinetics presented in <a href="#pathogens-13-00698-f003" class="html-fig">Figure 3</a>). Pearson correlation and <span class="html-italic">p</span>-values calculated using Minitab (v18); linear fit performed using Origin (v2019b).</p> Full article ">Figure 5
<p>Far-UVC inactivation data collected through the systematised literature review showing 1-Log<sub>10</sub> ID value (mJ·cm<sup>−2</sup>) for (<b>a</b>) vegetative cells and (<b>b</b>) endospores. Where 1-Log<sub>10</sub> ID is needed to be calculated for an individual species, the dose (mJ·cm<sup>−2</sup>) at which the greatest statistically significant inactivation was achieved prior to tailing was divided by the corresponding inactivation (Log<sub>10</sub> CFU·mL<sup>−1</sup>).</p> Full article ">Figure 6
<p>Graphs displaying data collected through systematised review for (<b>a</b>) bacterial cell density versus Far-UVC 1-Log<sub>10</sub> ID for all bacterial species, with data pertaining to at least three unique cell densities; (<b>b</b>) straight lines fitted using Origin (v2019b) to demonstrate relationship between cell density and Far-UVC 1-Log<sub>10</sub> ID for each individual bacterial species. * denotes significant Pearson correlation (<span class="html-italic">p</span> &lt; 0.05). All bacteria are in vegetative cell form.</p> Full article ">Figure 7
<p>Graphs displaying data collected through systematised review for (<b>a</b>) irradiance versus Far-UVC 1-Log<sub>10</sub> ID for all bacterial species with data pertaining to at least three unique irradiances; (<b>b</b>) straight lines fitted using Origin (v2019b) to demonstrate relationship between irradiance and 1-Log<sub>10</sub> ID for each individual bacterial species. Significant Pearson Correlation did not result in any case (<span class="html-italic">p</span> &lt; 0.05). All bacteria are in vegetative cell form unless specified otherwise.</p> Full article ">
45 pages, 5644 KiB  
Systematic Review
Tick-Borne Diseases in Sub-Saharan Africa: A Systematic Review of Pathogens, Research Focus, and Implications for Public Health
by Tidjani A. Djiman, Abel S. Biguezoton and Claude Saegerman
Pathogens 2024, 13(8), 697; https://doi.org/10.3390/pathogens13080697 - 17 Aug 2024
Viewed by 887
Abstract
Sub-Saharan Africa, with its hot and humid climate, is a conducive zone for tick proliferation. These vectors pose a major challenge to both animal and human health in the region. However, despite the relevance of emerging diseases and evidence of tick-borne disease emergence, [...] Read more.
Sub-Saharan Africa, with its hot and humid climate, is a conducive zone for tick proliferation. These vectors pose a major challenge to both animal and human health in the region. However, despite the relevance of emerging diseases and evidence of tick-borne disease emergence, very few studies have been dedicated to investigating zoonotic pathogens transmitted by ticks in this area. To raise awareness of the risks of tick-borne zoonotic diseases in sub-Saharan Africa, and to define a direction for future research, this systematic review considers the trends of research on tick-borne bacteria, parasites, and viruses from 2012 to 2023, aiming to highlight the circulation of these pathogens in ticks, cattle, sheep, goats, and humans. For this purpose, three international databases were screened to select 159 papers fitting designed inclusion criteria and used for qualitative analyses. Analysis of these studies revealed a high diversity of tick-borne pathogens in sub-Saharan Africa, with a total of 37 bacterial species, 27 parasite species, and 14 viruses identified. Among these, 27% were zoonotic pathogens, yet only 11 studies investigated their presence in humans. Furthermore, there is growing interest in the investigation of bacteria and parasites in both ticks and ruminants. However, research into viruses is limited and has only received notable interest from 2021 onwards. While studies on the detection of bacteria, including those of medical interest, have focused on ticks, little consideration has been given to these vectors in studies of parasites circulation. Regarding the limited focus on zoonotic pathogens transmitted by ticks, particularly in humans, despite documented cases of emerging zoonoses and the notable 27% proportion reported, further efforts should be made to fill these gaps. Future studies should prioritize the investigation of zoonotic pathogens, especially viruses, which represent the primary emerging threats, by adopting a One Health approach. This will enhance the understanding of their circulation and impact on both human and animal health. In addition, more attention should be given to the risk factors/drivers associated to their emergence as well as the perception of the population at risk of infection from these zoonotic pathogens. Full article
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<p>PRISMA flow diagram.</p> Full article ">Figure 2
<p>Number of studies according to types of pathogens.</p> Full article ">Figure 3
<p>Pathogens studies according to target population. Legend: “Screened” refers to the total number of studies that investigated the presence of each pathogen, regardless of whether the pathogen was detected or not. “Detected” indicates the number of studies in which the pathogen was actually detected.</p> Full article ">Figure 4
<p>Temporal evolution of studies on tick (<b>A</b>), animal (<b>B</b>), human (<b>C</b>), and combined (<b>D</b>) target populations.</p> Full article ">Figure 5
<p>Venn diagram of screened (<b>A</b>) and detected (<b>B</b>) pathogens in animals, ticks, and humans. Legend: “Screened” refers to the total number of studies that investigated the presence of each pathogen, regardless of whether the pathogen was detected or not. “Detected” indicates the number of studies in which the pathogen was actually detected.</p> Full article ">Figure 6
<p>Bacteria (<b>A</b>), parasite (<b>B</b>), and virus (<b>C</b>) families according to tick genus. Legend: “Screened” refers to the total number of studies that investigated the presence of each pathogen, regardless of whether the pathogen was detected or not. “Detected” indicates the number of studies in which the pathogen was actually detected.</p> Full article ">Figure 7
<p>Methods used to detect a domain’s pathogens in ticks (<b>A</b>), animals (<b>B</b>), and humans (<b>C</b>). Legend: This figure represents the number of times each method has been used to detect pathogens belonging to each pathogen domain (bacteria, parasites, and viruses) in ticks (<b>A</b>), animals (<b>B</b>), and humans (<b>C</b>). The various methods include the following: cPCR: conventional polymerase chain reaction; cPCR+sequencing: conventional polymerase chain reaction followed by the sequencing of the positive amplicons; nPCR: nested polymerase chain reaction; nPCR+sequencing: nested polymerase chain reaction followed by the sequencing of the positive amplicons; qPCR: quantitative polymerase chain reaction; qPCR+sequencing: quantitative polymerase chain reaction followed by the sequencing of the positive amplicons; RT_PCR: reverse transcription polymerase chain reaction; nRT_PCR: nested reverse transcription polymerase chain reaction; RT_PCR+sequencing: reverse transcription polymerase chain reaction followed by the sequencing of the positive amplicons; RT_qPCR: reverse transcription quantitative polymerase chain reaction; HRM_PCR: high-resolution melting polymerase chain reaction; HRM_PCR+sequencing: high-resolution melting polymerase chain reaction followed by the sequencing of the positive amplicons; LAMP: loop-mediated isothermal amplification; RLB: reverse line blot hybridization assay; and Metagenomic.</p> Full article ">Figure 8
<p>Distribution of tick-borne zoonotic bacteria and parasites in ticks (<b>A</b>), animals (<b>B</b>), and humans (<b>C</b>). Legend: These figures illustrate the geographical distribution and frequency of studies reporting the presence of zoonotic bacterial and parasitic agents transmitted by ticks in ticks (<b>A</b>), animals (<b>B</b>), and humans (<b>C</b>) in sub-Saharan Africa. Each pathogen is represented by a distinct color. The pie charts superimposed on the different countries indicate the frequency of studies reporting each pathogen in each country. The underlying map shows the average density of the ruminant population (cattle, sheep, goats) between 2012 and 2022, based on FAO statistics [<a href="#B36-pathogens-13-00697" class="html-bibr">36</a>]. The density is expressed as the number of animals per square mile.</p> Full article ">Figure 8 Cont.
<p>Distribution of tick-borne zoonotic bacteria and parasites in ticks (<b>A</b>), animals (<b>B</b>), and humans (<b>C</b>). Legend: These figures illustrate the geographical distribution and frequency of studies reporting the presence of zoonotic bacterial and parasitic agents transmitted by ticks in ticks (<b>A</b>), animals (<b>B</b>), and humans (<b>C</b>) in sub-Saharan Africa. Each pathogen is represented by a distinct color. The pie charts superimposed on the different countries indicate the frequency of studies reporting each pathogen in each country. The underlying map shows the average density of the ruminant population (cattle, sheep, goats) between 2012 and 2022, based on FAO statistics [<a href="#B36-pathogens-13-00697" class="html-bibr">36</a>]. The density is expressed as the number of animals per square mile.</p> Full article ">Figure 9
<p>Distribution of tick-borne viruses. Legend: The figure illustrates the geographical distribution and frequency of studies reporting the presence of viruses transmitted by ticks in in sub-Saharan Africa. Each virus is represented by a distinct color. The pie charts superimposed on the different countries indicate the frequency of studies reporting each virus in each country. The underlying map shows the average density of the ruminant population (cattle, sheep, goats) between 2012 and 2022, based on FAO statistics [<a href="#B36-pathogens-13-00697" class="html-bibr">36</a>]. The density is expressed as the number of animals per square mile. The red stars indicate a zoonotic virus; BDTPV: Brown dog tick phlebovirus; BOGV: Bogoria virus; PERV: Perkerra virus; JMTV: Jingmen tick virus; BPSV: Bovine papular stomatitis virus; PCPV: Pseudocowpox virus; KPTV: Kaptombes virus; BTV: Balanbala tick virus; BoTV: Bole tick virus.</p> Full article ">
8 pages, 811 KiB  
Communication
Risk of Ixodes ricinus Bites in a Population of Forestry Workers in an Endemic Region in France
by Antoine Grillon, Erik Sauleau and Nathalie Boulanger
Pathogens 2024, 13(8), 696; https://doi.org/10.3390/pathogens13080696 - 16 Aug 2024
Viewed by 528
Abstract
The progressing worldwide increases in tick occurrence and tick-borne diseases calls for the development of new prevention strategies to reduce their impact on human and animal health. Defining the risk of exposure to tick bites is therefore essential. Forestry workers are at high [...] Read more.
The progressing worldwide increases in tick occurrence and tick-borne diseases calls for the development of new prevention strategies to reduce their impact on human and animal health. Defining the risk of exposure to tick bites is therefore essential. Forestry workers are at high risk of tick bites. We set up an explorative study among forestry workers in the Alsace region in eastern France to measure the different factors affecting the risk of Ixodes ricinus tick bites during their activities in forests. For one year, forestry workers recorded the presence of ticks on their clothes and tick bites every time they were working in teams in different forest ecosystems. Questions about the prevention measures they followed were also noted. Among the 32 participants, we were able to differentiate between groups having a high, neutral, or low risk of being bitten. The median tick bite number per year was 4 (0–8). We tried to identify individual as well as environmental factors affecting the risk of tick bites. Factors influencing the risk were the seasonal peak of tick activity in May and June, the time of exposure, and the forest ecosystems visited during the year. Additional factors potentially affecting the risk were also identified. Full article
(This article belongs to the Topic Ticks and Tick-Borne Pathogens)
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<p>Risk of tick bites according to the month of the year, including the 2015–2016 and 2018–2019 studies, using a Poisson regression model.</p> Full article ">Figure 2
<p>The attraction rates (number of ticks per hour of outing for each participant) for three clusters of tick bite risk, ‘low’, ‘neutral’ and ‘high’, determined using Poisson regression model.</p> Full article ">
14 pages, 286 KiB  
Review
Approaches for Targeting Naegleria fowleri Using Nanoparticles and Artificial Peptides
by Hayley Fong, Zachary H. Leid and Anjan Debnath
Pathogens 2024, 13(8), 695; https://doi.org/10.3390/pathogens13080695 - 16 Aug 2024
Viewed by 842
Abstract
Naegleria fowleri is a free-living amoeba which causes primary amoebic meningoencephalitis (PAM). Although PAM is rare, the fatality rate is staggering at over 97%. So, the importance of finding an effective treatment and cure for PAM caused by N. fowleri is a crucial [...] Read more.
Naegleria fowleri is a free-living amoeba which causes primary amoebic meningoencephalitis (PAM). Although PAM is rare, the fatality rate is staggering at over 97%. So, the importance of finding an effective treatment and cure for PAM caused by N. fowleri is a crucial area of research. Existing research on developing novel therapeutic strategies to counter N. fowleri infection is limited. Since the blood–brain barrier (BBB) presents an obstacle to delivering drugs to the site of infection, it is important to employ strategies that can effectively direct the therapeutics to the brain. In this regard, our review focuses on understanding the physiology and mechanisms by which molecules pass through the BBB, the current treatment options available for PAM, and the recent research conducted in the decade of 2012 to 2022 on the use of nanomaterials to enhance drug delivery. In addition, we compile research findings from other central nervous system (CNS) diseases that use shuttle peptides which allow for transport of molecules through the BBB. The approach of utilizing BBB shuttles to administer drugs through the BBB may open up new areas of drug discovery research in the field of N. fowleri infection. Full article
(This article belongs to the Special Issue Free-Living Amoebae Infections)
8 pages, 432 KiB  
Article
Adding Hyponatremia to the “Rule-of-6” Prediction Tool Improves Performance in Identifying Hospitalised Patients with COVID-19 at Risk of Adverse Clinical Outcomes
by Meng Ying Sim, Jinghao Nicholas Ngiam, Matthew Chung Yi Koh, Wilson Goh, Srishti Chhabra, Nicholas W. S. Chew, Louis Yi Ann Chai, Paul Anantharajah Tambyah and Ching-Hui Sia
Pathogens 2024, 13(8), 694; https://doi.org/10.3390/pathogens13080694 - 16 Aug 2024
Viewed by 428
Abstract
The ‘rule-of-6’ prediction tool was shown to be able to identify COVID-19 patients at risk of adverse outcomes. During the pandemic, we frequently observed hyponatremia at presentation. We sought to evaluate if adding hyponatremia at presentation could improve the ‘rule-of-6’ prediction tool. We [...] Read more.
The ‘rule-of-6’ prediction tool was shown to be able to identify COVID-19 patients at risk of adverse outcomes. During the pandemic, we frequently observed hyponatremia at presentation. We sought to evaluate if adding hyponatremia at presentation could improve the ‘rule-of-6’ prediction tool. We retrospectively analysed 1781 consecutive patients admitted to a single tertiary academic institution in Singapore with COVID-19 infection from February 2020 to October 2021. A total of 161 (9.0%) patients had hyponatremia. These patients were significantly older, with more co-morbidities and more likely to be admitted during the Delta wave (2021). They were more likely to have radiographic evidence of pneumonia (46.0% versus 13.0%, p < 0.001) and more adverse outcomes (25.5% vs. 4.1%, p < 0.001). Hyponatremia remained independently associated with adverse outcomes after adjusting for age, lack of medical co-morbidities, vaccination status, year of admission, CRP, LDH, and ferritin. The optimised cut-off for serum sodium in predicting adverse outcomes was approximately <135 mmol/L as determined by the Youden index. Although derived in early 2020, the ‘rule-of-6’ prediction tool continued to perform well in our later cohort (AUC: 0.72, 95%CI: 0.66–0.78). Adding hyponatremia to the ‘rule-of-6’ improved its performance (AUC: 0.76, 95%CI: 0.71–0.82). Patients with hyponatremia at presentation for COVID-19 had poorer outcomes even as new variants emerged. Full article
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<p>Adding hyponatremia to the ‘rule-of-6’ prediction tool improves the area under the receiver operating characteristic curve in identifying patients at risk for adverse outcomes.</p> Full article ">
8 pages, 666 KiB  
Article
Glomerular Injury Is Associated with Severe Courses of Orthohantavirus Infection
by Christian Nusshag, Josephine Uhrig, Gefion Gruber, Pamela Schreiber, Martin Zeier and Ellen Krautkrämer
Pathogens 2024, 13(8), 693; https://doi.org/10.3390/pathogens13080693 - 16 Aug 2024
Viewed by 457
Abstract
Hemorrhagic fever with renal syndrome (HFRS) induced by Eurasian pathogenic orthohantaviruses is characterized by acute kidney injury (AKI) with often massive proteinuria. The mechanisms of the organ-specific manifestation are not completely understood. To analyze the role of glomerular and tubular damage in kidney [...] Read more.
Hemorrhagic fever with renal syndrome (HFRS) induced by Eurasian pathogenic orthohantaviruses is characterized by acute kidney injury (AKI) with often massive proteinuria. The mechanisms of the organ-specific manifestation are not completely understood. To analyze the role of glomerular and tubular damage in kidney injury induced by HFRS, we measured specific markers in urine samples of patients with acute Puumala virus (PUUV) infection and determined their correlation with disease severity. Levels of α1-microglobulin (α1-MG) and kidney injury molecule 1 (KIM-1), which is expressed by injured tubular epithelial cells, were measured to detect tubular dysfunction and injury. Immunoglobulin G (IgG) and the podocyte specific protein nephrin served as markers for glomerular injury. All four markers were elevated on admission. Markers of glomerular injury, IgG and nephrin, correlated with markers of disease severity such as length of hospitalization, serum creatinine, and proteinuria. In contrast, tubular injury did not correlate with these severity markers. Our results demonstrate that hantavirus infection induces both glomerular and tubular injury early in the clinical course. However, the glomerular dysfunction and podocyte injury seem to contribute directly to disease severity and to play a more central role in HFRS pathogenicity than direct damage to tubular epithelial cells. Full article
(This article belongs to the Section Viral Pathogens)
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<p>Urinary KIM-1 levels in patients with PUUV-HFRS (<span class="html-italic">n</span> = 22) on admission and a healthy age- and gender-matched control group (<span class="html-italic">n</span> = 10). Horizontal lines indicate means.</p> Full article ">Figure 2
<p>Levels of urinary KIM-1 were measured in patients with PUUV-HFRS (<span class="html-italic">n</span> = 12) on admission and 48 h after admission.</p> Full article ">Figure 3
<p>Course of urinary KIM-1 and nephrin levels and laboratory parameters in a patient with PUUV-HFRS. dpo: days post onset of symptoms.</p> Full article ">
20 pages, 1044 KiB  
Review
Advances in Engineering Circular RNA Vaccines
by Zhongyan Zhang, Yuanlei Fu, Xiaoli Ju, Furong Zhang, Peng Zhang and Meilin He
Pathogens 2024, 13(8), 692; https://doi.org/10.3390/pathogens13080692 - 15 Aug 2024
Viewed by 994
Abstract
Engineered circular RNAs (circRNAs) are a class of single-stranded RNAs with head-to-tail covalently linked structures that integrate open reading frames (ORFs) and internal ribosome entry sites (IRESs) with the function of coding and expressing proteins. Compared to mRNA vaccines, circRNA vaccines offer a [...] Read more.
Engineered circular RNAs (circRNAs) are a class of single-stranded RNAs with head-to-tail covalently linked structures that integrate open reading frames (ORFs) and internal ribosome entry sites (IRESs) with the function of coding and expressing proteins. Compared to mRNA vaccines, circRNA vaccines offer a more improved method that is safe, stable, and simple to manufacture. With the rapid revelation of the biological functions of circRNA and the success of Severe Acute Respiratory Coronavirus Type II (SARS-CoV-2) mRNA vaccines, biopharmaceutical companies and researchers around the globe are attempting to develop more stable circRNA vaccines for illness prevention and treatment. Nevertheless, research on circRNA vaccines is still in its infancy, and more work and assessment are needed for their synthesis, delivery, and use. In this review, based on the current understanding of the molecular biological properties and immunotherapeutic mechanisms of circRNA, we summarize the current preparation methods of circRNA vaccines, including design, synthesis, purification, and identification. We discuss their delivery strategies and summarize the challenges facing the clinical application of circRNAs to provide references for circRNA vaccine-related research. Full article
(This article belongs to the Section Vaccines and Therapeutic Developments)
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<p>Schematic diagram of in vitro artificial RNA cyclization methods. (<b>A</b>) Chemical synthesis. (<b>B</b>) Ligation by T4 RNA ligase. (<b>C</b>,<b>D</b>) The ribozymatic process used in in vitro cyclization to synthesize circRNA: (<b>C</b>) cyclization based on type I intron PIE system, (<b>D</b>) cyclization based on type II intron self-splicing.</p> Full article ">Figure 2
<p>Structure diagram of circRNA delivery system. The delivery vectors from (<b>A</b>–<b>E</b>) are naked circRNA direct delivery, LNP, exosome, hydrogel, and protamine.</p> Full article ">
21 pages, 1816 KiB  
Review
Mosquito Gut Microbiota: A Review
by Hongmei Liu, Jianhai Yin, Xiaodan Huang, Chuanhui Zang, Ye Zhang, Jianping Cao and Maoqing Gong
Pathogens 2024, 13(8), 691; https://doi.org/10.3390/pathogens13080691 - 15 Aug 2024
Viewed by 664
Abstract
Mosquitoes are vectors of many important human diseases. The prolonged and widespread use of insecticides has led to the development of mosquito resistance to these insecticides. The gut microbiota is considered the master of host development and physiology; it influences mosquito biology, disease [...] Read more.
Mosquitoes are vectors of many important human diseases. The prolonged and widespread use of insecticides has led to the development of mosquito resistance to these insecticides. The gut microbiota is considered the master of host development and physiology; it influences mosquito biology, disease pathogen transmission, and resistance to insecticides. Understanding the role and mechanisms of mosquito gut microbiota in mosquito insecticide resistance is useful for developing new strategies for tackling mosquito insecticide resistance. We searched online databases, including PubMed, MEDLINE, SciELO, Web of Science, and the Chinese Science Citation Database. We searched all terms, including microbiota and mosquitoes, or any specific genera or species of mosquitoes. We reviewed the relationships between microbiota and mosquito growth, development, survival, reproduction, and disease pathogen transmission, as well as the interactions between microbiota and mosquito insecticide resistance. Overall, 429 studies were included in this review after filtering 8139 search results. Mosquito gut microbiota show a complex community structure with rich species diversity, dynamic changes in the species composition over time (season) and across space (environmental setting), and variation among mosquito species and mosquito developmental stages (larval vs. adult). The community composition of the microbiota plays profound roles in mosquito development, survival, and reproduction. There was a reciprocal interaction between the mosquito midgut microbiota and virus infection in mosquitoes. Wolbachia, Asaia, and Serratia are the three most studied bacteria that influence disease pathogen transmission. The insecticide resistance or exposure led to the enrichment or reduction in certain microorganisms in the resistant mosquitoes while enhancing the abundance of other microorganisms in insect-susceptible mosquitoes, and they involved many different species/genera/families of microorganisms. Conversely, microbiota can promote insecticide resistance in their hosts by isolating and degrading insecticidal compounds or altering the expression of host genes and metabolic detoxification enzymes. Currently, knowledge is scarce about the community structure of mosquito gut microbiota and its functionality in relation to mosquito pathogen transmission and insecticide resistance. The new multi-omics techniques should be adopted to find the links among environment, mosquito, and host and bring mosquito microbiota studies to the next level. Full article
(This article belongs to the Special Issue Prevalence, Molecular Characterization and Mechanism of Antiparasitic Resistance)
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<p>Flowchart of the article search and screening process.</p> Full article ">Figure 2
<p>Environments involved in mosquito development and tools and methods for the analysis of mosquito microbiota.</p> Full article ">Figure 3
<p>Some of the key areas for mosquito microbiota studies.</p> Full article ">
19 pages, 4746 KiB  
Article
Baculovirus-Assisted Production of Bartonella bacilliformis Proteins: A Potential Strategy for Improving Serological Diagnosis of Carrion’s Disease
by Lizbeth Sally Vilca-Machaca, Karen Daphne Calvay-Sanchez, Yanina Zarate-Sulca, Victor Jimenez-Vasquez, Pablo Ramirez and Giovanna Mendoza-Mujica
Pathogens 2024, 13(8), 690; https://doi.org/10.3390/pathogens13080690 - 15 Aug 2024
Viewed by 652
Abstract
Carrion’s disease, caused by Bartonella bacilliformis, is a neglected tropical disease prevalent in the Andean region of South America. Without antimicrobial treatment, this disease has a mortality rate of up to 88% in infected patients. The most common method for diagnosing B. [...] Read more.
Carrion’s disease, caused by Bartonella bacilliformis, is a neglected tropical disease prevalent in the Andean region of South America. Without antimicrobial treatment, this disease has a mortality rate of up to 88% in infected patients. The most common method for diagnosing B. bacilliformis infection is serological testing. However, the current serological assays are limited in sensitivity and specificity, underscoring the need for the development of novel and more accurate diagnostic tools. Recombinant proteins have emerged as promising candidates to improve the serological diagnosis of Carrion’s disease. So, we focused on evaluating the conditions for producing two previously predicted proteins of B. bacilliformis using the baculovirus–insect cell expression system, mainly the flashBAC ULTRA technology. We assessed various parameters to identify the conditions that yield the highest protein production, including cell lines, temperature, and hours post-infection (hpi). The results showed that the expression conditions for achieving the highest yields of the Prot_689 and Prot_504 proteins were obtained using High Five™ cells at 21 °C and harvesting at 120 hpi. Subsequently, the seroreactivity of recombinant proteins was evaluated using positive sera from patients diagnosed with Carrion’s disease. These findings offer valuable insights into the production conditions of B. bacilliformis recombinant proteins using the baculovirus system, which could significantly contribute to developing more precise diagnostic tools for Carrion’s disease. Therefore, this research provides implications for improving diagnostics and potentially developing therapeutic strategies. Full article
(This article belongs to the Special Issue Emerging and Re-emerging Bacterial Infections)
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<p>PCR analysis of recombinant plasmids. Image of bands obtained on 1.8% agarose gel for the visualization of PCR products.</p> Full article ">Figure 2
<p>Domain mapping and expressed regions of recombinant proteins (<b>A</b>) RlpA and (<b>B</b>) BamA. SP: signal peptide. RlpA: Rare lipoprotein A. POTRA: Polypeptide Transport-Associated. aas: amino acids.</p> Full article ">Figure 3
<p>Temporal analysis of Sf9 cell response to transfection. (<b>A</b>) Sf9 control cells at 5 h post-infection (hpi). (<b>B</b>,<b>C</b>) Transfected Sf9 cells at 5 hpi. (<b>D</b>) Sf9 control cells 5 days after the assay initiation. (<b>E</b>,<b>F</b>) Transfected Sf9 cells at 5 days post-infection (dpi). (<b>G</b>) Sf9 control cells 7 days after the assay initiation. (<b>H</b>,<b>I</b>) Transfected Sf9 cells at 7 dpi. Observed with a 40× inverted microscope.</p> Full article ">Figure 4
<p>Higher expression of recombinant protein Prot_689 in High Five™ cells compared to Sf9: Western blot analysis of cellular pellet fractions using anti-His tag HRP-conjugated antibody.</p> Full article ">Figure 5
<p>Comparative expression of recombinant protein Prot_504 in High Five™ and Sf9 cells: Western blot analysis of cellular pellet fractions using anti-His tag HRP-conjugated antibody.</p> Full article ">Figure 6
<p>SDS-PAGE analysis of purified pellet fractions of Prot_689 and Prot_504 expressed in High Five™ cells: polyacrylamide gel, 15% stained with Coomassie blue R-250. M: protein marker. C: High Five™ cell control. T: total protein. PP: protein post-purification.</p> Full article ">Figure 7
<p>Western blot analysis of purified pellet fractions of Prot_689 and Prot_504 expressed in High Five™ cells: specific detection with anti-His tag antibody. M: protein marker. C: High Five™ cell control. T: total protein. PP: protein post-purification.</p> Full article ">Figure 8
<p>Evaluation of seroreactivity using Western blot: nitrocellulose membranes impregnated with (<b>A</b>) Prot_689 and (<b>B</b>) Prot_504 for assessing immunological activity of selected proteins. M: protein marker. H: anti-His tag antibody. S+: human serum positive for Carrion‘s disease. SB: serum positive for brucellosis. S−: negative human serum.</p> Full article ">Figure A1
<p>(<b>a</b>) Map of the pBAC-1+Prot_689 plasmid. (<b>b</b>) Map of the pBAC-1+Prot_504 plasmid. Both plasmids feature the gene of interest within the blue region.</p> Full article ">
11 pages, 1768 KiB  
Article
Large-Scale Serological Survey of Crimean-Congo Hemorrhagic Fever Virus and Rift Valley Fever Virus in Small Ruminants in Senegal
by Marie Cicille Ba Gahn, Gorgui Diouf, Ndjibouyé Cissé, Mamadou Ciss, Marion Bordier, Mbengué Ndiaye, Mame Thierno Bakhoum, Mamadou Lamine Djiba, Corrie Brown, Bonto Faburay, Assane Gueye Fall and Modou Moustapha Lo
Pathogens 2024, 13(8), 689; https://doi.org/10.3390/pathogens13080689 - 15 Aug 2024
Viewed by 761
Abstract
Crimean-Congo hemorrhagic fever (CCHF) and Rift Valley fever (RVF) are among the list of emerging zoonotic diseases that require special attention and priority. RVF is one of the six priority diseases selected by the Senegalese government. Repeated epidemic episodes and sporadic cases of [...] Read more.
Crimean-Congo hemorrhagic fever (CCHF) and Rift Valley fever (RVF) are among the list of emerging zoonotic diseases that require special attention and priority. RVF is one of the six priority diseases selected by the Senegalese government. Repeated epidemic episodes and sporadic cases of CCHF and RVF in Senegal motivated this study, involving a national cross-sectional serological survey to assess the distribution of the two diseases in this country throughout the small ruminant population. A total of 2127 sera from small ruminants (goat and sheep) were collected in all regions of Senegal. The overall seroprevalence of CCHF and RVF was 14.1% (IC 95%: 12.5–15.5) and 4.4% (95% CI: 3.5–5.3), respectively. The regions of Saint-Louis (38.4%; 95% CI: 30.4–46.2), Kolda (28.3%; 95% CI: 20.9–35.7), Tambacounda (22.2%; 95% CI: 15.8–28.6) and Kédougou (20.9%; 95% CI: 14.4–27.4) were the most affected areas. The risk factors identified during this study show that the age, species and sex of the animals are key factors in determining exposure to these two viruses. This study confirms the active circulation of CCHF in Senegal and provides important and consistent data that can be used to improve the surveillance strategy of a two-in-one health approach to zoonoses. Full article
(This article belongs to the Special Issue Diagnostics of Emerging and Re-emerging Pathogens)
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<p>Map of sampling sites in 14 regions of Senegal.</p> Full article ">Figure 2
<p>Spatial distribution of CCHFV seroprevalence of small ruminants in Senegal.</p> Full article ">Figure 3
<p>Spatial distribution of RVFV seroprevalence of small ruminants in Senegal.</p> Full article ">
10 pages, 2776 KiB  
Article
A Retrospective Study of Genetic Characterization in Suspected Visceral Leishmaniasis Cases in Greece, 2005 to 2020
by Maria Evangelidou, Sofia Makka, Ioanna Papadogiannaki, Myrto Koutantou, Nikolaos Tegos, Anastasia Mpimpa, Eleni Patsoula and Emmanouil Angelakis
Pathogens 2024, 13(8), 688; https://doi.org/10.3390/pathogens13080688 - 14 Aug 2024
Viewed by 574
Abstract
Leishmania infantum is considered the predominant Leishmania species responsible for visceral leishmaniasis (VL) in Greece but limited molecular-typing-based studies have been performed so far. We retrospectively analyzed data and serum samples collected from 3661 individuals suspected for VL in a sixteen-year period, from 2005 [...] Read more.
Leishmania infantum is considered the predominant Leishmania species responsible for visceral leishmaniasis (VL) in Greece but limited molecular-typing-based studies have been performed so far. We retrospectively analyzed data and serum samples collected from 3661 individuals suspected for VL in a sixteen-year period, from 2005 to 2020, to study the seasonality and demographic characteristics of VL cases and to define the L. infantum genotypes circulating in the country. Serum samples were tested with immunofluorescence assay and/or molecular assay. qPCR Leishmania-positive samples were subjected to genotypic analysis based on polymorphisms in 12 microsatellite regions of the internal transcribed spacers (ITSs) 1 and 2. We diagnosed 219 definite (6%, sample with a positive molecular assay and/or antibody titer ≥ 1:400) and 230 probable (6.3%, sample with antibody titer between 1:100 and 1:200) VL cases. Data analysis revealed that amongst VL-definite cases, the age group (≥65) constitutes the most affected factor, since 36.9% of the VL cases belonged to this age group. Amongst the VL definite cases, the most frequently reported symptoms were fever (83%), splenomegaly (49%), and hepatomegaly (40%), but this was not the case for immunocompromised patients that developed non-typical symptoms of leishmaniasis. Although no statistically significant differences in the overall seasonality of VL cases were observed, February and June showed a significantly higher proportion of VL cases compared to August and December. Genotyping of ITS1 and ITS2 regions revealed that all VL cases belong to ITS type A of L. infantum. Our study provides epidemiological information on VL and demonstrates for the first time, providing genotypic data, the circulation of ITS type A L. infantum in Greece. Full article
(This article belongs to the Special Issue One Health: New Approaches, Research and Innovation to Zoonoses)
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<p>Total number of patients tested and distribution of proportion of VL cases across months for the sixteen-year period 2005–2020. * <span class="html-italic">p</span> &lt; 0.05; ** <span class="html-italic">p</span> &lt; 0.005.</p> Full article ">Figure 2
<p>Sequencing and phylogenetic analysis of <span class="html-italic">L infantum</span> based on ITS regions. (<b>A</b>) Alignment of ITS reference types and one representative of 16 Greek isolates. Red boxes indicate absolute similarity of one representative Greek isolate with ITS Type A. (<b>B</b>) Phylogenetic relationships of <span class="html-italic">L. donovani</span> complex strains and 16 Greek isolates. The phylogenetic tree was constructed by using the maximum-likelihood method based on the Tamura–Nei substitution model. Colored bullets show the species and corresponding geographical regions of ITS type origins.</p> Full article ">
21 pages, 3543 KiB  
Article
Identifying the Drivers Related to Animal Reservoirs, Environment, and Socio-Demography of Human Leptospirosis in Different Community Types of Southern Chile: An Application of Machine Learning Algorithm in One Health Perspective
by Himel Talukder, Claudia Muñoz-Zanzi, Miguel Salgado, Sergey Berg and Anni Yang
Pathogens 2024, 13(8), 687; https://doi.org/10.3390/pathogens13080687 - 14 Aug 2024
Viewed by 591
Abstract
Leptospirosis is a zoonosis with global public health impact, particularly in poor socio-economic settings in tropical regions. Transmitted through urine-contaminated water or soil from rodents, dogs, and livestock, leptospirosis causes over a million clinical cases annually. Risk factors include outdoor activities, livestock production, [...] Read more.
Leptospirosis is a zoonosis with global public health impact, particularly in poor socio-economic settings in tropical regions. Transmitted through urine-contaminated water or soil from rodents, dogs, and livestock, leptospirosis causes over a million clinical cases annually. Risk factors include outdoor activities, livestock production, and substandard housing that foster high densities of animal reservoirs. This One Health study in southern Chile examined Leptospira serological evidence of exposure in people from urban slums, semi-rural settings, and farm settings, using the Extreme Gradient Boosting algorithm to identify key influencing factors. In urban slums, age, shrub terrain, distance to Leptospira-positive households, and neighborhood housing density were contributing factors. Human exposure in semi-rural communities was linked to environmental factors (trees, shrubs, and lower vegetation terrain) and animal variables (Leptospira-positive dogs and rodents and proximity to Leptospira-positive households). On farms, dog counts, animal Leptospira prevalence, and proximity to Leptospira-contaminated water samples were significant drivers. The study underscores that disease dynamics vary across landscapes, with distinct drivers in each community setting. This case study demonstrates how the integration of machine learning with comprehensive cross-sectional epidemiological and geospatial data provides valuable insights into leptospirosis eco-epidemiology. These insights are crucial for informing targeted public health strategies and generating hypotheses for future research. Full article
(This article belongs to the Special Issue One Health and Neglected Zoonotic Diseases)
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<p>Study area and distribution of leptospirosis seropositive (purple) and seronegative (blue) participants across the various community types indicated by shape (semi-rural: circle, farm: square, urban slums: triangle).</p> Full article ">Figure 2
<p><span class="html-italic">Leptospira</span> positivity distribution in rodents (PCR kidney carriage positivity), domestic animals (MAT seropositivity), water (PCR positivity), and people among MAT seropositivity (<b>A</b>) by community type and (<b>B</b>) in each of the 12 communities, three within each community type. Darker color in a bar represents the proportion of individuals with a MAT titer ≥ 1:400.</p> Full article ">Figure 3
<p>Variable importance plot for the model results of the three community types: (<b>A</b>) urban slums, (<b>B</b>) semi-rural, and (<b>C</b>) farm. Variables with more than a 2% importance frequency score have been shown. The bars were color-coded for ease of interpretation of the overall trend in the predicted relationship between each variable and human exposure probability across the three different community types. Note that the relationship types depicted here were derived visually from <a href="#pathogens-13-00687-f004" class="html-fig">Figure 4</a>, <a href="#pathogens-13-00687-f005" class="html-fig">Figure 5</a> and <a href="#pathogens-13-00687-f006" class="html-fig">Figure 6</a> and were simplified to overall positive or negative, but actual relationships are non-linear.</p> Full article ">Figure 4
<p>The partial dependency plots of covariates used in the model for urban slum communities. The gray shading area indicates the confidence intervals derived from the model iterations. The variable importance score is reported in the parentheses ((<b>A</b>–<b>N</b>): partial dependency of each variable in the model).</p> Full article ">Figure 5
<p>The partial dependency plots of covariates used in the model for semi-rural communities. The gray shading area indicates the confidence intervals derived from the model iterations. The variable importance score is reported in the parentheses ((<b>A</b>–<b>N</b>): partial dependency of each variable in the model).</p> Full article ">Figure 6
<p>The partial dependency plots of covariates used in the model for farm communities. The gray shading area indicates the confidence intervals derived from the model iterations. The variable importance score is reported in the parentheses ((<b>A</b>–<b>M</b>): partial dependency of each variable in the model).</p> Full article ">
7 pages, 257 KiB  
Communication
High Prevalence of Syphilis among Young Pregnant Women in the Brazilian Amazon: A Cross-Sectional Study Based on Clinical Records in a Public Health Reference Unit in the City of Belém
by Ana Paula Figueiredo de Montalvão França, Camille Massena de Sousa, Misma Suely Gonçalves Araújo de Lima, Ricardo Roberto de Souza Fonseca, Rogério Valois Laurentino, Jacqueline Cortinhas Monteiro, Rosimar Neris Mantins Feitosa, Leonardo Miranda dos Santos, Aldemir Branco Oliveira-Filho and Luiz Fernando Almeida Machado
Pathogens 2024, 13(8), 686; https://doi.org/10.3390/pathogens13080686 - 14 Aug 2024
Viewed by 433
Abstract
Background: Syphilis remains a significant global public health concern, and one of its consequences in pregnant women is the potential occurrence of congenital syphilis due to Treponema pallidum infection. This study determined the prevalence of syphilis among pregnant women undergoing prenatal care in [...] Read more.
Background: Syphilis remains a significant global public health concern, and one of its consequences in pregnant women is the potential occurrence of congenital syphilis due to Treponema pallidum infection. This study determined the prevalence of syphilis among pregnant women undergoing prenatal care in a neighborhood on the outskirts of the city of Belém, Brazilian Amazon. Methods: This cross-sectional study used data from clinical records of 611 pregnant women who underwent prenatal care at a public health unit in 2019 and 2020. The reagent result for VDRL was used as an indicator of syphilis. Odds Ratio and chi-square tests were used to evaluate the association of information from pregnant women with syphilis. Results: The overall prevalence of syphilis was 5.2 % (32/611; 95 % CI: 3.5–7.0 %). Age under 23 years was identified as a risk factor for syphilis. Conclusions: The prevalence of syphilis among pregnant women in the outskirts of Belém is high, especially among younger women. There is an urgent need to intensify innovative sexual and reproductive health education initiatives and emphasize the importance of consistent practice of preventive measures against syphilis and other STIs in the Amazon region, especially in the young population. Full article
(This article belongs to the Special Issue Sexually Transmitted Pathogens and Associated Infections, Diseases, Syndromes, and Complications)
21 pages, 339 KiB  
Review
Advancing Public Health Surveillance: Integrating Modeling and GIS in the Wastewater-Based Epidemiology of Viruses, a Narrative Review
by Diego F. Cuadros, Xi Chen, Jingjing Li, Ryosuke Omori and Godfrey Musuka
Pathogens 2024, 13(8), 685; https://doi.org/10.3390/pathogens13080685 - 14 Aug 2024
Viewed by 605
Abstract
This review article will present a comprehensive examination of the use of modeling, spatial analysis, and geographic information systems (GIS) in the surveillance of viruses in wastewater. With the advent of global health challenges like the COVID-19 pandemic, wastewater surveillance has emerged as [...] Read more.
This review article will present a comprehensive examination of the use of modeling, spatial analysis, and geographic information systems (GIS) in the surveillance of viruses in wastewater. With the advent of global health challenges like the COVID-19 pandemic, wastewater surveillance has emerged as a crucial tool for the early detection and management of viral outbreaks. This review will explore the application of various modeling techniques that enable the prediction and understanding of virus concentrations and spread patterns in wastewater systems. It highlights the role of spatial analysis in mapping the geographic distribution of viral loads, providing insights into the dynamics of virus transmission within communities. The integration of GIS in wastewater surveillance will be explored, emphasizing the utility of such systems in visualizing data, enhancing sampling site selection, and ensuring equitable monitoring across diverse populations. The review will also discuss the innovative combination of GIS with remote sensing data and predictive modeling, offering a multi-faceted approach to understand virus spread. Challenges such as data quality, privacy concerns, and the necessity for interdisciplinary collaboration will be addressed. This review concludes by underscoring the transformative potential of these analytical tools in public health, advocating for continued research and innovation to strengthen preparedness and response strategies for future viral threats. This article aims to provide a foundational understanding for researchers and public health officials, fostering advancements in the field of wastewater-based epidemiology. Full article
(This article belongs to the Special Issue Viruses in Water)
5 pages, 196 KiB  
Perspective
Central Nervous System Disorders of Marine Mammals: Models for Human Disease?
by Giovanni Di Guardo
Pathogens 2024, 13(8), 684; https://doi.org/10.3390/pathogens13080684 - 14 Aug 2024
Viewed by 828
Abstract
This article deals with Central Nervous System (CNS) disorders of marine mammals as putative neuropathology and neuropathogenesis models for their human and, to some extent, their animal “counterparts” in a dual “One Health” and “Translational Medicine” perspective. Within this challenging context, special emphasis [...] Read more.
This article deals with Central Nervous System (CNS) disorders of marine mammals as putative neuropathology and neuropathogenesis models for their human and, to some extent, their animal “counterparts” in a dual “One Health” and “Translational Medicine” perspective. Within this challenging context, special emphasis is placed upon Alzheimer’s disease (AD), provided that AD-like pathological changes have been reported in the brain tissue of stranded cetacean specimens belonging to different Odontocete species. Further examples of potential comparative pathology interest are represented by viral infections and, in particular, by “Subacute Sclerosing Panencephalitis” (SSPE), a rare neurologic sequela in patients infected with Measles virus (MeV). Indeed, Cetacean morbillivirus (CeMV)-infected striped dolphins (Stenella coeruleoalba) may also develop a “brain-only” form of CeMV infection, sharing neuropathological similarities with SSPE. Within this framework, the global threat of the A(H5N1) avian influenza virus is another major concern issue, with a severe meningoencephalitis occurring in affected pinnipeds and cetaceans, similarly to what is seen in human beings. Finally, the role of Brucella ceti-infected, neurobrucellosis-affected cetaceans as putative neuropathology and neuropathogenesis models for their human disease counterparts is also analyzed and discussed. Notwithstanding the above, much more work is needed before drawing the conclusion marine mammal CNS disorders mirror their human “analogues”. Full article
(This article belongs to the Section Emerging Pathogens)
11 pages, 556 KiB  
Article
Missed Opportunities for HIV Diagnosis and Their Clinical Repercussions in the Portuguese Population—A Cohort Study
by João Lourinho, Maria João Miguel, Frederico Gonçalves, Francisco Vale, Cláudia Silva Franco and Nuno Marques
Pathogens 2024, 13(8), 683; https://doi.org/10.3390/pathogens13080683 - 13 Aug 2024
Viewed by 594
Abstract
Late human immunodeficiency virus (HIV) diagnosis has been associated with missed opportunities for earlier diagnosis. We conducted a retrospective, longitudinal, single-centre cohort study evaluating these missed opportunities and their clinical repercussions in adults with a new HIV diagnosis or who were drug-naïve, who [...] Read more.
Late human immunodeficiency virus (HIV) diagnosis has been associated with missed opportunities for earlier diagnosis. We conducted a retrospective, longitudinal, single-centre cohort study evaluating these missed opportunities and their clinical repercussions in adults with a new HIV diagnosis or who were drug-naïve, who attended our Infectious Diseases Department between 2018 and 2023. We assessed missed opportunities in the two years prior to diagnosis or after the last negative HIV test. We compared clinical and laboratorial data from individuals with and without missed opportunities. The primary outcome considered was AIDS-defining conditions at diagnosis. Among the 436 included individuals, 27.1% experienced at least one missed opportunity. Those with missed opportunities were more likely to be female (p = 0.007), older at their first consultation (p < 0.001), born in Africa (p < 0.001) and in countries with a high HIV prevalence (p < 0.001), and have heterosexual transmission (p < 0.001). The adjusted analysis showed that missed opportunities were significantly associated with AIDS-defining conditions at diagnosis (OR 3.23, CI 95% [1.62–6.46], p < 0.001). These findings highlight the impact of missed opportunities on HIV severity, underscoring the need for more targeted interventions to reduce them. Full article
(This article belongs to the Special Issue HIV/AIDS: Epidemiology, Drug Resistance, Treatment and Prevention)
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<p>Flowchart of inclusion and exclusion process.</p> Full article ">
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