Persistent Infection Research Articles

Evaluation of The Effectiveness of HIV Prevention Strategies on HIV Prevalence Among Men and Women in Zoba-Ma’akel/Eritrea

Human Immunodeficiency Virus (HIV) emerged in the late 1970s and is transmitted through unprotected sex, mother-to-child transmission, drug use and contaminated medical tools. HIV have continued yet, as health and development problems through the world. This study assesses the effectiveness of HIV prevention strategies in Zoba-Ma’akel/ Eritrea, focusing on gender disparities in HIV prevalence. Using Convergent-Parallel-Mixed-Method of Research Design, the study gathered quantitative data from 150 people living with HIV, and qualitative data from experts and community leaders. The quantitative data were processed using SPSS, while qualitative data were analyzed in thematic and content-based methods. The study found a significant decline in HIV prevalence in Zoba-Ma’akel over the past decade, but noted persistent new infections and higher prevalence among women. Key findings highlighted the importance of HIV education, the impact of gender-based violence, stigma, unemployment and the effectiveness of Antiretroviral Therapy. Innovative strategies, such as establishment of Association for People Living with HIV, couple testing, and integrated HIV-TB prevention, were identified as crucial. The study recommended targeted interventions for high-risk groups and emphasized the need for women's empowerment programs. Despite challenges, the study provided valuable insights for policymakers and future research

Dual‐Crosslinked Antibacterial Hydrogel for Treatment of Diabetic Foot Ulcers

AbstractDiabetic foot ulcer has become a heavy burden to the healthcare system with the high and growing incidence of diabetes. Persistent bacterial infections in diabetic wounds can lead to chronic inflammation and delayed wound healing. To address these challenges, a dual‐crosslinked antibacterial hydrogel loaded with anti‐inflammatory compound asiaticoside is developed in this study. The hydrogel demonstrated suitable gelation properties, good biocompatibility, and exceptional antibacterial activity. In a diabetic foot ulcer model on rats, the asiaticoside‐loaded hydrogel can alleviate inflammation, promote angiogenesis, and accelerate wound healing. Therefore, this asiaticoside‐loaded antibacterial hydrogel shows considerable potential for diabetic wound healing.

Revision of ex vivo endodontic biofilm model using computer aided design

ObjectiveMost endodontic diseases are bacterium-mediated inflammatory or necrotic process induced by contaminated dental pulp. Although great advances are being performed to obtain more efficient antibacterial strategies for persistent infections, most studies lack of representative models to test their antibacterial effects and their outcomes cannot be promptly translated to clinical practice. Therefore, this study aimed to refine an ex vivo endodontic biofilm model combining human tooth, computer guided design and 3D printing to obtain a more reproducible and predictable model. MethodsMonoradicular teeth were cut using three different methods: hand-held (HCC), mechanical precision (MPC) and computer aid guided cutting (CGC). Then, blocks were reassembled. The different model preparations were assessed in terms of dimensional tolerance, surface analysis, liquid tightness and Enterococcus faecalis biofilm development for 21 days, which was studied by metabolic assays and confocal microscopy. Then, the proposed model was validated using different commercial disinfecting treatments. ResultsCGC exhibited significantly lower deviation and surface without defects compared to HHC and MPC, leading to superior liquid tightness. Similarly, mature biofilms with high metabolic activity and vitality were observed in all conditions, CGC showing the lowest variation. Regarding the model validation, all antibacterial treatments resulted in the complete eradication of bacteria in the standard 2D model, whereas commercial treatments exhibited varying levels of efficacy in the proposed ex vivo model, from moderately reduction of metabolic activity to complete elimination of biofilm. ConclusionsThe novel guided approach represents a more reliable, standardized, and reproducible model for the evaluation of endodontic disinfecting therapies. Clinical SignificanceDuring antibacterial treatment development, challenging 3D models using teeth substrates to test antibacterial treatments novel guided approach represents a more reliable, standardized, and reproducible model for the evaluation of endodontic disinfecting therapies.

Antibacterial properties of photo-crosslinked chitosan/methacrylated hyaluronic acid nanoparticles loaded with bacitracin

The current treatments for wounds often fail to induce adequate healing, leaving wounds vulnerable to persistent infections and development of drug-resistant microbial biofilms. New natural-derived nanoparticles were studied to impair bacteria colonization and hinder the formation of biofilms in wounds. The nanoparticles were fabricated through polyelectrolyte complexation of chitosan (CS, polycation) and hyaluronic acid (HA, polyanion). UV-induced photo-crosslinking was used to enhance the stability of the nanoparticles. To achieve this, HA was methacrylated (HAMA, degree of modification of 20 %). Photo-crosslinked nanoparticles obtained from HAMA and CS had a diameter of 478 nm and a more homogeneous size distribution than nanoparticles assembled solely through complexation (742 nm). The nanoparticles were loaded with the antimicrobial agent bacitracin (BC), resulting in nanoparticles with a diameter of 332 nm. The encapsulation of BC was highly efficient (97 %). The BC-loaded nanoparticles showed significant antibacterial activity against gram-positive bacteria Staphylococcus aureus, Methicillin-resistant S. aureus and S. epidermidis. Photo-crosslinked HAMA/CS nanoparticles loaded with BC demonstrated inhibition of biofilm formation and a positive effect on the proliferation of mammalian cells (L929). These crosslinked nanoparticles have potential for the long-term treatment of wounds and controlled antibiotic delivery at the location of a lesion.

Tricalcium phosphate-loaded injectable hydrogel as a promising osteogenic and bactericidal teicoplanin-delivery system for osteomyelitis treatment: An in vitro and in vivo investigation

Osteomyelitis is an inflammation of bone tissue usually caused by pyogenic bacteria. The most recurrent clinical approach consists of bone debridement followed by parenteral administration of antibiotics. However, systemic antibiotic treatment has limitations regarding absorption rate and bioavailability over time. The main challenge of osteomyelitis treatment consists of coupling the persistent infection treatment with the regeneration of the bone debrided. In this work, we developed an injectable drug delivery system based on poloxamer 407 hydrogel containing undoped Mg, Zn-doped tricalcium phosphate (β-TCP), and teicoplanin, a broad-spectrum antibiotic. We evaluated how the addition of teicoplanin and β-TCP affected the micellization, gelation, particle size, and surface charge of the hydrogel. Later, we studied the hydrogel degradation and drug delivery kinetics. Finally, the bactericidal, biocompatibility, and osteogenic properties were evaluated through in vitro studies and confirmed by in vivo Wistar rat models. Teicoplanin was found to be encapsulated in the corona portions of the hydrogel micelles, yielding a bigger hydrodynamics radius. The encapsulated teicoplanin showed a sustained release over the evaluated period, enough to trigger antibacterial properties against Gram-positive bacteria. Besides, the formulations were biocompatible and showed bone healing ability and osteogenic properties. Finally, in vivo studies confirmed that the proposed locally injected formulations yielded osteomyelitis treatment with superior outcomes than parenteral administration while promoting bone regeneration. In conclusion, the presented formulations are promising drug delivery systems for osteomyelitis treatment and deserve further technological improvements.

DNA damage response and inflammatory response: Two traffic lights for HPVs on the road to transformation.

Human papillomaviruses (HPVs) are non-enveloped double-stranded DNA viruses. When HPV infection persists, infected tissues can develop many HPV-related diseases such as cervical cancer and head and neck squamous cell carcinoma. To establish their persistent infection, HPVs have evolved mechanisms to manipulate the host cellular processes such as DNA damage response (DDR), which includes homologous recombination, nonhomologous end joining, and microhomology-mediated end joining. Additionally, HPVs utilize host inflammatory processes to facilitate their life cycles. Here, we bridge the concepts of DDR and inflammatory response, and discuss how HPV proteins orchestrate a sophisticated manipulation of DDR and inflammation to promote their viral replication, ultimately fostering the progression of infected cells towards oncogenic transformation to malignancy.

Unraveling the molecular regulation of biofilm underlying effect of chronic disease medications.

A biofilm is a complex microbial structure that promotes the progression of persistent infections, particularly in nosocomial settings via indwelling medical devices. Conventional antibiotics are often ineffective treatments for biofilms; hence, it is crucial to investigate or design non-antibiotic antibiofilm compounds that can successfully reduce and eradicate biofilm-related infections. This study was an attempt to repurpose chronic disease medications of the antihypertensive and antilipidemic drug classes, including candesartan cilexetil (CC) and ursodeoxycholic acid (UDCA), respectively, to be used as antibiofilm agents against the two infectious pathogens Staphylococcus aureus and Enterococcus faecalis. Crystal violet (CV) staining assay was used to evaluate the antibiofilm activity of the drugs. Real-time polymerase chain reaction (RT-PCR) was performed to determine the transcription levels of the biofilm-related genes (icaA and icaR in S. aureus and fsrC and gelE in E. faecalis) following treatment with different concentrations of CC and UDCA. we found that a concentration of greater than 1.5 µg/ml of CC significantly (p < 0.005) inhibited the biofilm formation of both bacterial isolates, and a concentration of greater than 50 µg/ml of UDCA significantly (p < 0.005) inhibited the biofilm formation of both bacterial isolates. Interestingly, the mRNA expression levels of biofilm-related genes were decreased in the two bacterial isolates at concentrations that were lower than the human pharmaceutical daily doses.

Knee fusion versus above knee amputation as two options to deal with knee periprosthetic joint infection.

Periprosthetic joint infection (PJI) poses a significant challenge in total knee arthroplasty (TKA), with recurrence rates as high as 14-28%, leading to substantial morbidity and treatment costs. When conventional treatments fail, knee fusion and above-the-knee amputation (AKA) emerge as alternative options. Existing literature offers conflicting views on the efficacy and impact of knee fusion versus AKA with varied outcomes and limitations. This retrospective national study spanning 2010-2022 investigates Knee Fusion and AKA as options for addressing Knee PJI. Utilizing PearlDiver Patient Records Database, procedural, and reimbursement data on over 100million individuals from all the US was evaluated. Readmission rates, costs, and complications of the mentioned procedures were assessed using ICD-9 and ICD-10 codes within a 90-day period and one-year post-operation. Statistical analyses, including chi-square tests and regression models, were conducted using integrated R software. The study reveals a substantial escalation (p < 0.0001) in the proportion of patients opting for AKA compared to arthrodesis. While age as a demographic factor showed no significant difference, arthrodesis patients exhibited lower comorbidity scores (3.6 ± 2.9 vs. 4.6 ± 3.4, p < 0.001). Arthrodesis correlated with higher 90-day thromboembolism rates (9.2% vs. 7.3%, p < 0.001), blood transfusion requirements (23.2% vs. 14.4%, p < 0.001), and acute renal failure incidence (p = 0.008) but demonstrated lower rates of urinary tract infections (p = 0.047) and cerebrovascular accidents (p < 0.001). At 1 year, arthrodesis was associated with higher infection rates (38.7% vs. 36.4%, p < 0.001). Arthrodesis patients had significant increased 90-day and 1-year readmission rates and hospitalization costs ($12,732 vs. $18,826, p < 0.001). We found higher rates of 1-year thromboembolism, infection, acute renal failure, and readmission in the arthrodesis group. AKA patients had more sepsis and cerebrovascular accidents. A patient-centered conversation is best for persistent infections and failed revision TKA. Considering the patient's quality of life, goals, and health status, this discussion should cover each procedure's risks and complications.

Neutrophil Extracellular Traps-Inspired Bismuth-Based Polypeptide Nanonets for Synergetic Treatment of Bacterial Infections.

Excessive use of antibiotics and the formation of bacterial biofilms can lead to persistent infections caused by drug-resistant bacteria, rendering ineffective immune responses and even life-threatening. There is an urgent need to explore synergistic antibacterial therapies across all stages of infection. Drawing inspiration from the antibacterial properties of neutrophil extracellular traps (NETs) and integrating the bacterial biofilm dispersal mechanism involving boronic acid-catechol interaction, the multifunctional bismuth-based polypeptide nanonets (PLBA-Bi-Fe-TA) are developed. These nanonets are designed to capture bacteria through a coordination complex involving cationic polypeptides (PLBA) with boronic acid-functionalized side chains, alongside metal ions (bismuth (Bi) and iron (Fe)), and tannic acid (TA). Leveraging the nanoconfinement-enhanced high-contact network-driven multiple efficiency, PLBA-Bi-Fe-TA demonstrates the excellent ability to swiftly capture bacteria and their extracellular polysaccharides. This interaction culminates in the formation of a highly hydrophilic complex, effectively enabling the rapid inhibition and dispersion of antibiotic-resistant bacterial biofilms, while Fe-TA shows mild photothermal ability to further assist fluffy mature biofilm. In addition, Bi is beneficial to regulate the polarization of macrophages to pro-inflammatory phenotype to further kill escaping biofilm bacteria. In summary, this novel approach offers a promising bionic optimization strategy for treating bacterial-associated infections at all stages through synergetic treatment.

A Crosstalk Analysis of high-risk human papillomavirus, microbiota and vaginal metabolome in cervicovaginal microenvironment

The microbial community has a profound effect on the host microenvironment by altering metabolites. Persistent high-risk human papillomavirus (HRHPV) infection has been implicated as contributors to the initiation and progression of cervical cancer, but the involved mechanisms are unknown. Assessing the metabolic profile of the cervicovaginal microenvironment has the potential to reveal the functional interactions among the host, metabolites and microbes in HRHPV persistence infection and progression to cancer. The vaginal swabs of women were collected and divided into three groups according to the HPV HybridenPture DNA test (HC2). The participants, include 9 who were categorized as HPV-negative, 8 as positive for HPV16, and 9 as positive for HPV18. 16S rRNA gene sequencing and metabolomics analyses were applied to determine the influence of the vaginal microbiota and host metabolism on the link between HPV and cervicovaginal microenvironment. These findings revealed that HRHPV groups have unique metabolic fingerprints that distinguish them from heathy controls. We showed that HRHPV affects changes in microbial metabolic function, which has important implications for the host. Our study further demonstrated metabolite-driven complex host-microbe interactions and assist in understanding the alterations in the HRHPV-induced cervicovaginal microenvironment.

Helicobacter pylori infection increases the risk of dyslipidemia in Chinese diabetic Population: a retrospective cross-sectional study

BackgroundIn contemporary times, increased prevalence of Helicobacter pylori (H. pylori) infection and elevated dyslipidemia levels present substantial public health challenges. However, the relationship between H. pylori and dyslipidemia remains inconclusive. No studies have yet conducted a population-based classification to investigate the impact of H. pylori infection on dyslipidemia in individuals with diabetes.MethodsA retrospective cohort study was carried out on a total of 60,535 individuals who underwent health check-ups at the Health Examination Center in Taizhou Hospital from 2017 to 2022. Physical measurements, hematological markers and detection of H. pylori were gathered from all patients. The study population was further stratified into diabetic and non-diabetic groups for analysis.ResultsH. pylori infection was found to be an autonomous risk factor for dyslipidemia based on the results of multivariate logistic regression analysis (OR = 1.13, 95% CI: 1.03–1.24). However, no notable effect on dyslipidemia in the non-diabetic group was observed. Furthermore, at the follow-up, the group with persistent negative showed a significantly lower incidence ratio of dyslipidemia compared to the group with persistent infection (P = 0.006). The persistent negative group exhibited a significantly higher rate of improvement in dyslipidemia compared to the new infection group (P = 0.038).ConclusionsIn the diabetic population, the presence of H. pylori infection heightens the propensity for developing dyslipidemia. Therefore, the implementation of efficient eradication strategies for H. pylori infection could potentially lead to a decrease in the occurrence of dyslipidemia among individuals with diabetes.

Harnessing Machine Learning to Uncover Hidden Patterns in Azole-Resistant CYP51/ERG11 Proteins.

Fungal resistance is a public health concern due to the limited availability of antifungal resources and the complexities associated with treating persistent fungal infections. Azoles are thus far the primary line of defense against fungi. Specifically, azoles inhibit the conversion of lanosterol to ergosterol, producing defective sterols and impairing fluidity in fungal plasmatic membranes. Studies on azole resistance have emphasized specific point mutations in CYP51/ERG11 proteins linked to resistance. Although very insightful, the traditional approach to studying azole resistance is time-consuming and prone to errors during meticulous alignment evaluation. It relies on a reference-based method using a specific protein sequence obtained from a wild-type (WT) phenotype. Therefore, this study introduces a machine learning (ML)-based approach utilizing molecular descriptors representing the physiochemical attributes of CYP51/ERG11 protein isoforms. This approach aims to unravel hidden patterns associated with azole resistance. The results highlight that descriptors related to amino acid composition and their combination of hydrophobicity and hydrophilicity effectively explain the slight differences between the resistant non-wild-type (NWT) and WT (nonresistant) protein sequences. This study underscores the potential of ML to unravel nuanced patterns in CYP51/ERG11 sequences, providing valuable molecular signatures that could inform future endeavors in drug development and computational screening of resistant and nonresistant fungal lineages.

Biomarker-Based Analysis of Pain in Patients with Tick-Borne Infections before and after Antibiotic Treatment.

Tick-borne illnesses (TBIs), especially those caused by Borrelia, are increasingly prevalent worldwide. These diseases progress through stages of initial localization, early spread, and late dissemination. The final stage often leads to post-treatment Lyme disease syndrome (PTLDS) or chronic Lyme disease (CLD), characterized by persistent and non-specific multisystem symptoms affecting multiple systems, lasting over six months after antibiotic therapy. PTLDS significantly reduces functional ability, with 82-96% of patients experiencing pain, including arthritis, arthralgia, and myalgia. Inflammatory markers like CRP and TNF-alpha indicate ongoing inflammation, but the link between chronic pain and other biomarkers is underexplored. This study examined the relationship between pain and biomarkers in TBI patients from an Irish hospital and their response to antibiotic treatment. Pain ratings significantly decreased after antibiotic treatment, with median pain scores dropping from 7 to 5 (U = 27215.50, p < 0.001). This suggests a persistent infection responsive to antibiotics. Age and gender did not influence pain ratings before and after treatment. The study found correlations between pain ratings and biomarkers such as transferrin, CD4%, platelets, and neutrophils. However, variations in these biomarkers did not significantly predict pain changes when considering biomarkers outside the study. These findings imply that included biomarkers do not directly predict pain changes, possibly indicating allostatic load in symptom variability among long-term TBI patients. The study emphasizes the need for appropriate antibiotic treatment for TBIs, highlighting human rights issues related to withholding pain relief.

Comparative Assessment of Gutta-Percha Removal Techniques for Endodontic Retreatment: Efficiency and Clinical Implications

Background: Endodontic retreatment involves the removal of gutta-percha and sealer from root canals to address treatment failures and persistent infections. This study aimed to systematically evaluate and compare the effectiveness of different gutta-percha removal techniques.Methods: Sixty extracted human teeth with single canals were selected. The canals were initially treated, obturated with gutta-percha, and divided into six groups (n=10 each). Each group represented a distinct removal technique: rotary instrument-driven, Gates-Glidden drill-assisted, solvent-based dissolution, ultrasonic removal, heat-based softening, and a control group. Gutta-percha mass and canal wall cleanliness were assessed post-removal. Statistical analyses were performed using ANOVA and post hoc Tukey's HSD tests.Results: The solvent-based dissolution technique exhibited the most efficient removal, achieving the lowest mean remaining gutta-percha mass (0.89 ± 0.15 mg) and the highest canal wall cleanliness (95% ± 3%). The ultrasonic technique also showed effective removal capabilities with a mean remaining mass of 1.56 ± 0.22 mg and a cleanliness of 89% ± 4%. The rotary technique resulted in a mean mass of 2.47 ± 0.30 mg and cleanliness of 84% ± 5%. Gates-Glidden drill-assisted and heat-based techniques showed moderate performance with remaining masses of 3.18 ± 0.25 mg and 2.10 ± 0.20 mg, respectively, and cleanliness percentages of 78% ± 6% and 81% ± 5%. The control group had the highest remaining mass (9.88 ± 0.42 mg) and the lowest cleanliness (10% ± 2%), confirming the efficacy of the removal techniques.Conclusion: The solvent-based dissolution technique demonstrated superior efficacy in gutta-percha removal. Ultrasonic and rotary techniques were also effective choices. Clinicians should consider these findings when selecting gutta-percha removal methods for endodontic retreatment procedures.Keywords: Endodontic retreatment; Gutta-Percha removal; Canal wall cleanliness; Comparative efficacy; Removal techniques

A Study to evaluate Oral Candidal Colonization and Species Variation in Diabetes Patients

Introduction Diabetes mellitus is a clinical syndrome characterized by hyperglycemia due to absolute or relative deficiency of insulin. In the oral cavity, yeasts commonly colonize the tongue, palate, and buccal mucosa. Aside from oral mucosa, recent research have revealed the existence of C. albicans in other oral sites such as root canal, including persistent infection, carious lesions, and periodontal pockets5. The main aim of the study is to evaluate and compare Candidal colonization and species variation in healthy individuals and Diabetic patients. Material &amp; Methods Study includes 60 samples which are divided into Group –I consist of 30 Diabetic patients &amp; Group II consists of 30 healthy individuals. Blood samples were collected to estimate the glucose levels using Glucose Tolerance Test &amp; HbA1C. Saliva Sample was collected to estimate the candida using VITEK_2 Procedure. The absorbance values were measured on a digital calorimeter for Glucose Tolerance Test &amp; HbA1C levels using the standard protocol. Results Statistical Analysis was done using SPS software. Anova test &amp; Paired t –test were done to estimate the comparison of Candidal positivity to HbA1C and VITEK_2 Procedure showed a mean of 97.33 and SD of 11.02 and with that of HbA1C, showed a mean of 4.93 and SD of 1.00. Comparison of study &amp; control groups with VITEK2 status showed (46%) Candida albicans, followed by (16.67%) Candida famata and (10%) Candida tropicalis. Conclusion The patients with diabetes mellitus are at a higher risk of developing oral Candidiasis. These members of the normal flora probably acquire invasiveness and become pathogenic leading to change in disease progression and develop resistance to the existing drug regime. Key Words: Diabetes mellitus, Glucose, Hyperglycemia, Oral candidasis, Lesions etc.

Traditional Chinese Medicine Erhuang Suppository for Treatment of Persistent High-risk Human Papillomavirus Infection and Its Impact on Transcriptome of Uterine Cervix.

High-risk human papillomavirus (HR-HPV) infection is the chief cause of cervical intraepithelial neoplasia (CIN) and cervical carcinoma. The Erhuang suppository (EHS) is a traditional Chinese medicine (TCM) prepared from realgar (As2S2), Coptidis rhizoma, alumen, and borneolum syntheticum and has been used for antiviral and antitumor purposes. However, whether EHS can efficiently alleviate HR-HPV infection remains unclear. This study was conducted to evaluate the efficacy of EHS for the treatment of persistent HR-HPV infection in the uterine cervix. In this study, we evaluated the therapeutic efficacy of EHS in a randomized controlled clinical trial with a 3-month follow-up. Totally, 70 patients with persistent HR-HPV infection were randomly assigned to receive intravaginal administration of EHS or placebo. HPV DNA, ThinPrep cytologic test (TCT), colposcopy, and safety evaluation were carried out after treatment. Microarray analysis was performed to compare transcriptome profiles before and after EHS treatment. A K14-HPV16 mouse model was generated to confirm the efficiency of EHS. After 3 months, 74.3% (26/35) of the patients in the treatment group were HPV negative, compared to 6.9% (2/29) in the placebo group. High-throughput microarrays revealed distinct transcriptome profiles after treatment. The differentially expressed genes were significantly enriched in complement activation, immune response, and apoptotic processes. The K14-HPV16 mouse model also validated the remarkable efficacy of EHS. This study demonstrated that EHS is effective against HR-HPV infection and cervical lesions. Additionally, no obvious systemic toxicity was observed in patients during the trial. The superior efficacy and safety of EHS demonstrated its considerable value as a potential cost-effective drug for the treatment of HPV infection and HPV-related cervical diseases.

FlagT4G Vaccine Prevents Transplacental Transmission of Highly Virulent Classical Swine Fever Virus after Single Vaccination in Pregnant Sows.

The transplacental transmission of CSFV and the resulting persistent congenital infection in newborn piglets have been abundantly discussed in pregnant sows suffering from virus infection. Importantly, the availability of safe commercial vaccines with proven efficacy to prevent the generation of congenital and postnatal persistent infections in pregnant sows are critical tools for controlling the disease in CSF endemic areas. Here, we demonstrate the high efficacy of a single dose of the recombinant FlagT4G vaccine to provide solid protection in pregnant sows against transplacental transmission of a highly virulent CSFV. Pregnant sows vaccinated with FlagT4G at 44 days of gestation elicited a strong CSFV-specific antibody response, with neutralizing antibody levels above those required for protection against CSFV. Importantly, after the challenge with a highly virulent CSFV, all foetuses from FlagT4G-vaccinated sows lacked CSF macroscopic lesions and showed a complete absence of the challenge virus in their internal organs at day 79 of gestation. Therefore, pregnant sows safely vaccinated with FlagT4G without affecting reproductive efficacy are efficaciously protected, along with their foetuses, against the infection and disease caused by a CSFV virulent field strain.

Association between heavy metals exposure and persistent infections: the mediating role of immune function.

Persistent infections caused by certain viruses and parasites have been associated with multiple diseases and substantial mortality. Heavy metals are ubiquitous environmental pollutants with immunosuppressive properties. This study aimed to determine whether heavy metals exposure suppress the immune system, thereby increasing the susceptibility to persistent infections. Using data from NHANES 1999-2016, we explored the associations between heavy metals exposure and persistent infections: Cytomegalovirus (CMV), Epstein-Barr Virus (EBV), Hepatitis C Virus (HCV), Herpes Simplex Virus Type-1 (HSV-1), Toxoplasma gondii (T. gondii), and Toxocara canis and Toxocara cati (Toxocara spp.) by performing logistic regression, weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) models. Mediation analysis was used to determine the mediating role of host immune function in these associations. Logistic regression analysis revealed positive associations between multiple heavy metals and the increased risk of persistent infections. In WQS models, the heavy metals mixture was associated with increased risks of several persistent infections: CMV (OR: 1.58; 95% CI: 1.17, 2.14), HCV (OR: 2.94; 95% CI: 1.68, 5.16), HSV-1 (OR: 1.25; 95% CI: 1.11, 1.42), T. gondii (OR: 1.97; 95% CI: 1.41, 2.76), and Toxocara spp. (OR: 1.76; 95% CI: 1.16, 2.66). BKMR models further confirmed the combined effects of heavy metals mixture and also identified the individual effect of arsenic, cadmium, and lead. On mediation analysis, the systemic immune inflammation index, which reflects the host's immune status, mediated 12.14% of the association of mixed heavy metals exposure with HSV-1 infection. The findings of this study revealed that heavy metals exposure may increase susceptibility to persistent infections, with the host's immune status potentially mediating this relationship. Reducing exposure to heavy metals may have preventive implications for persistent infections, and further prospective studies are needed to confirm these findings.

The evaluation of risk factors for prolonged viral shedding during anti-SARS-CoV-2 monoclonal antibodies and long-term administration of antivirals in COVID-19 patients with B-cell lymphoma treated by anti-CD20 antibody

BackgroundThe global impact of the coronavirus disease 2019 (COVID-19) pandemic has resulted in significant morbidity and mortality. Immunocompromised patients, particularly those treated for B-cell lymphoma, have shown an increased risk of persistent infection with SARS-CoV-2 and severe outcomes and mortality. Multi-mutational SARS-CoV-2 variants can arise during the course of such persistent cases of COVID-19. No optimal, decisive strategy is currently available for patients with persistent infection that allows clinicians to sustain viral clearance, determine optimal timing to stop treatment, and prevent virus reactivation. We introduced a novel treatment combining antivirals, neutralizing antibodies, and genomic analysis with frequent monitoring of spike-specific antibody and viral load for immunocompromised patients with persistent COVID-19 infection. The aim of this retrospective study was to report and evaluate the efficacy of our novel treatment for immunocompromised B-cell lymphoma patients with persistent COVID-19 infection.MethodsThis retrospective descriptive analysis had no controls. Patients with B-cell lymphoma previously receiving immunotherapy including anti-CD20 antibodies, diagnosed as having COVID-19 infection, and treated in our hospital after January 2022 were included. We selected anti-SARS-CoV-2 monoclonal antibodies according to subvariants. Every 5 days, viral load was tested by RT-PCR, with antivirals continued until viral shedding was confirmed. Primary outcome was virus elimination. Independent predictors of prolonged viral shedding time were determined by multivariate Cox regression.ResultsForty-four patients were included in this study. Thirty-five patients received rituximab, 19 obinutuzumab, and 26 bendamustine. Median treatment duration was 10 (IQR, 10–20) days; 22 patients received combination antiviral therapy. COVID-19 was severe in 16 patients, and critical in 2. All patients survived, with viral shedding confirmed at median 28 (IQR, 19–38) days. Bendamustine use or within 1 year of last treatment for B-cell lymphoma, and multiple treatment lines for B-cell lymphoma significantly prolonged time to viral shedding.ConclusionsAmong 44 consecutive patients treated, anti-SARS-CoV-2 monoclonal antibodies and long-term administration of antiviral drugs, switching, and combination therapy resulted in virus elimination and 100% survival. Bendamustine use, within 1 year of last treatment for B-cell lymphoma, and multiple treatment lines for B-cell lymphoma were the significant independent predictors of prolonged viral shedding time.

Is It Useful to Repeat Blood Cultures in Endocarditis Patients? A Critical Appraisal.

Previous guidelines for endocarditis have suggested repeating blood cultures until they become negative, with limited evidence. Literature reviews were conducted (1) on the incidence of persistent bacteremia and association with outcome and (2) on timing of valve culture negativization to examine the claim for prolongation of antibiotic therapy starting from negative blood cultures. Persistent bacteremia and fever may be present in the first 3 days of endocarditis, despite treatment, and are more common in Staphylococcus (especially MRSA) and Enterococcus species. Persistent bacteremia (48-72 h), persistent infection (day 7), and new onset septic shock are related and predict in-hospital mortality. It is, however, persistent infection at day 7 and septic shock that primarily determine the infectious course of endocarditis, and not persistent bacteremia. Valve cultures at surgery become negative in most cases (>85-90%) after 14-21 days of antibiotic therapy, with no calculated benefit for prolonging therapy after 21 days. Persistent infection at 7 days after appropriate antibiotic therapy is a better key event for prognosis then positive or negative blood cultures at 48-72 h. Therapy prolongation from the day of negative blood cultures is not reasonable. There is no need to survey blood cultures in endocarditis patients after starting therapy.