Decrease In Titer Research Articles

Porcine low-density lipoprotein receptor plays an important role in classical swine fever virus infection

ABSTRACT Several cellular factors have been reported to be required for replication of classical swine fever virus (CSFV), a member of the genus Pestivirus within the family Flaviviridae. However, many steps of its replication cycle are still poorly understood. The low-density lipoprotein receptor (LDLR) is involved in cell entry and post-entry processes of different viruses including other members of the Flaviviridae. In this study, the relevance of LDLR in replication of CSFV and another porcine pestivirus, Bungowannah pestivirus (BuPV), was investigated by antibody-mediated blocking of LDLR and genetically engineered porcine cell lines providing altered LDLR expression levels. An LDLR-specific antibody largely blocked infection with CSFV, but had only a minor impact on BuPV. Infections of the genetically modified cells confirmed an LDLR-dependent replication of CSFV. Compared to wild type cells, lower and higher expression of LDLR resulted in a 3.5-fold decrease or increase in viral titers already 20 h post infection. Viral titers were 25-fold increased in LDLR-overexpressing cells compared to cells with reduced LDLR expression at 72 h post infection. The varying LDLR expression levels had no clear effect on permissivity to BuPV. A decoy receptor assay using recombinant soluble LDLR provided no evidence that LDLR may function as a receptor for CSFV or BuPV. Differences in their dependency on LDLR suggest that CSFV and BuPV likely use different mechanisms to interact with their host cells. Moreover, this study reveals similarities in the replication cycles of CSFV and other members of the family Flaviviridae that are dependent on LDLR.

Post-therapeutic cure criterion in chronic Chagas disease using Trypanosoma cruzi chimeric proteins.

Chagas disease (CD) is a neglected disease caused by Trypanosoma cruzi Chagas, 1909. Causative treatment can be achieved with two drugs: benznidazole or Nifurtimox. There are some gaps that hinder progress in eradicating the disease. There is no test that can efficiently assess cure control after treatment. Currently, the decline in anti-T. cruzi antibody titres is assessed with conventional serological tests, which can take years. However, the search for new markers of cure must continue to fill this gap. The present study aimed to evaluate the decline in serological titres using chimeric proteins after treatment with benznidazole in chronic patients diagnosed with CD. It was a prospective cross-sectional cohort study between 2000 and 2004 of T. cruzi-positive participants from the Añatuya region (Argentina) treated with benznidazole. Serum samples from ten patients were collected before treatment (day zero) and after the end of treatment (2, 3, 6, 12, 24 and 36 months). For the detection of anti-T. cruzi antibodies, an indirect ELISA was performed using two chimeric recombinant proteins (IBMP-8.1 and IBMP-8.4) as antigens. The changes in reactivity index within the groups before and after treatment were evaluated using the Friedman test. All participants experienced a decrease in serological titres after treatment with benznidazole, especially IBMP-8.1. However, due to the small number of samples and the short follow-up period, it is premature to conclude that this molecule serves as a criterion for sustained cure. Further studies are needed to validate tests based on these or other biomarkers to demonstrate parasitological cure.

Rituximab may affect T lymphocyte subsets balance in primary membranous nephropathy

BackgroundThe aim of this study was to investigate the effects and significance of rituximab (RTX) on the levels of T lymphocyte subsets in patients diagnosed with primary membranous nephropathy (PMN).MethodsA total of 58 PMN patients and 25 healthy donors were chosen as the subjects. Among the PMN patients, 40 individuals received RTX treatment and completed at least 6 months of follow-up. All subjects underwent flow cytometry analysis to determine the peripheral blood lymphocyte subsets. The changes in anti-PLA2R antibody titers and 24-hour urinary protein levels were evaluated by ELISA and Biuret method before and after treatment.Results(1) The PMN group exhibited a significantly greater percentage of peripheral blood CD3−CD19+ B cells than the healthy group, which is consistent with the findings of previous reports. Additionally, compared with those in the peripheral blood of healthy individuals, the numbers of CD4+ central memory T cells, CD4+ effector memory T cells, CD4+/CD8+, and CD4+CD25+ T cells in the PMN peripheral blood were markedly greater. However, the number of peripheral blood Treg cells was reduced in the PMN group. (2) After 6 months of RTX treatment, PMN patients exhibited significant decreases in anti-PLA2R antibody titers, 24-hour urinary protein levels, and peripheral blood CD3−CD19+ B cells. Importantly, RTX administration decreased CD4+CD25+ T cells and CD4+/CD8+ in the peripheral blood of PMN patients and improved Treg cell levels. (3) RTX treatment induced alterations in the CD4+ T lymphocyte subsets in PMN patients, which did not correlate with B lymphocyte counts or anti-PLA2R antibody titers.ConclusionsRTX treatment might have a beneficial impact on cellular immunity by effectively restoring the balance of CD4+ T lymphocyte subsets in PMN patients, which is beyond its effects on B cells and antibody production.Trial registrationThe research was registered at the First Affiliated Hospital of Soochow University. Registration Number: MR-32-23-016211. Registration Date: May 31, 2023.

Stability study in selected conditions and biofilm-reducing activity of phages active against drug-resistant Acinetobacter baumannii.

Acinetobacter baumannii is currently a serious threat to human health, especially to people with immunodeficiency as well as patients with prolonged hospital stays and those undergoing invasive medical procedures. The ever-increasing percentage of strains characterized by multidrug resistance to widely used antibiotics and their ability to form biofilms make it difficult to fight infections with traditional antibiotic therapy. In view of the above, phage therapy seems to be extremely attractive. Therefore, phages with good storage stability are recommended for therapeutic purposes. In this work, we present the results of studies on the stability of 12 phages specific for A. baumannii under different conditions (including temperature, different pH values, commercially available disinfectants, essential oils, and surfactants) and in the urine of patients with urinary tract infections (UTIs). Based on our long-term stability studies, the most optimal storage method for the A. baumannii phage turned out to be - 70°C. In contrast, 60°C caused a significant decrease in phage activity after 1 h of incubation. The tested phages were the most stable at a pH from 7.0 to 9.0, with the most inactivating pH being strongly acidic. Interestingly, ethanol-based disinfectants caused a significant decrease in phage titers even after 30s of incubation. Moreover, copper and silver nanoparticle solutions also caused a decrease in phage titers (which was statistically significant, except for the Acba_3 phage incubated in silver solution), but to a much lesser extent than disinfectants. However, bacteriophages incubated for 24h in essential oils (cinnamon and eucalyptus) can be considered stable.

Infliximab desensitization in patients with inflammatory bowel diseases: a safe therapeutic alternative

Background Hypersensitivity reactions (HSR) to the administration of infliximab (IFX) in Inflammatory Bowel Diseases (IBD) patients are not rare and usually lead to drug discontinuation. We report data on safety and effectiveness of desensitization to IFX in patients with previous HSR. Methods We conducted a retrospective monocentric observational study. Patients for whom a desensitization protocol to IFX was realized after a previous HSR were included. Anti-drug antibodies (ADA) and IFX trough levels at both inclusion and six months after desensitization were collected. Clinical outcomes, including recurrence of HSR were evaluated. Results From 2005 to 2020, 27 patients (Crohn’s Disease: 26 (96%) were included). Desensitization after HSR was performed after a median time of 10.4 months (2.9-33.1). Nineteen (70%) patients received immunosuppressants at time of desensitization. Eight (30%) patients presented HSR at first (n = 2), second (n = 4) or third (n = 2) IFX perfusion after desensitization. None led to intensive care unit transfer or death. Thirteen (48%) had clinical response at 6 months and 8 (29%) were still under IFX treatment two years after desensitization. IFX trough levels and ADA were available for 14 patients at time of desensitization. Most patients (12 out of 14) had ADA at a high level. At 6 months, among the 7 patients with long term response to IFX, 4 presented a decrease of ADA titers and 2 had a significant trough level of IFX. Conclusion IFX desensitization in patients with IBD is a safe therapeutic alternative and represents a potential option for patients refractory to multiple biologics. What is already known? Hypersensitivity reactions to the administration of infliximab is frequent. Occurrence of hypersensitivity reaction, either immediate or delayed, usually leads to permanent drug discontinuation. What is new here? Infliximab desensitization is well tolerated with no hypersensitivity reaction recurrence in 70% of patients. Clinical success at 6 months was of 48% and around a third of patients remained under infliximab therapy two years after desensitization. Antidrug antibodies decreased and infliximab trough levels increased in these patients showing the impact of desensitization on immunogenicity. How can this study help patient care? Infliximab desensitization represents a potential option for patients refractory to multiple biologics who presented hypersensitivity reaction to the drug.

In vitro inhibition of rotavirus multiplication by copper oxide nanoparticles.

Group A rotaviruses are the most common cause of gastroenteritis in children under five years of age worldwide. Rotavirus gastroenteritis can be related to mild to severe diarrhea in children and in some cases, can lead to death due to severe dehydration. Approximately 146,480 people die annually from rotavirus infection worldwide, and most of these deaths occur in low-income countries in Africa and Asia. Since there are no specific effective drugs to treat rotavirus infections, and infected patients can only be treated supportively, new antiviral agents need to be developed. Copper oxide nanoparticles (CuO NPs) have a wide range of applications in the magnetic and electrical industries, as well as in biology. The antiviral activity of nanoparticles (CuO NPs) is well documented. This study aimed to investigate the antiviral effect of CuO NPs on rotaviruses. The cytotoxic effects of CuO NPs on MA-104 cells were examined by methyl thiazolyl tetrazolium assay. In addition, the anti-rotavirus activity of CuO NPs was evaluated by TCID50 and real-time polymerase chain reaction PCR assay. Our results showed that exposure of rotavirus-infected cells to various non-toxic concentrations of CuO NPs did not cause a decrease in viral titer, compared to the control. However, the virucidal effect of CuO NPs on rotavirus was observed at concentrations of 80 and 100 μg/ml (P<0.001). Our study suggested that CuO NPs had significant antiviral activity against rotavirus replication. However, the exact mechanism of anti-rotavirus activity of CuO NPs remained unknown. According to the virucidal assay, it appears that the loss of capsid integrity and genome disruption in the presence of CuO NPs are possible mechanisms of its anti-rotavirus activity.

Heat inactivation of aqueous viable norovirus and MS2 bacteriophage.

This study aimed to compare the heat inactivation kinetics of viable human norovirus with the surrogate, MS2 bacteriophage as well as assess the decay of the RNA signal. Human intestinal enteroids were used to analyze the heat inactivation kinetics of viable human norovirus compared to the surrogate MS2 bacteriophage, which was cultured using a plaque assay. Norovirus decay rates were 0.22 min-1, 0.68 min-1, and 1.11 min-1 for 50°C, 60°C, and 70°C, respectively, and MS2 bacteriophage decay rates were 0.0065 min-1, 0.045 min-1, and 0.16 min-1 for 50°C, 60°C, and 70°C, respectively. Norovirus had significantly higher decay rates than MS2 bacteriophage at all tested temperatures (P=.002-.007). No decrease of RNA titers as measured by reverse transcription-PCR for both human norovirus and MS2 bacteriophage over time was observed, indicating molecular methods do not accurately depict viable human norovirus after heat inactivation and treatment efficiency is underestimated. Overall, our data demonstrate that MS2 bacteriophage is a conservative surrogate to measure heat inactivation and potentially overestimates the infectious risk of norovirus. Furthermore, this study corroborates that measuring viral RNA titers, as evaluated by PCR methods, does not correlate with the persistence of viable norovirus under heat inactivation.

P921 Maintenance of clinical, biochemical and transmural remission in inflammatory bowel disease patients switching from intravenous to subcutaneous infliximab

Abstract Background Subcutaneous (SC) infliximab (IFX) effectively maintains biochemical, clinical and endoscopic remission in inflammatory bowel disease (IBD) with a comparable safety profile to intravenous (IV) formulation. Transmural healing is considered a desirable long-term treatment endpoint in IBD, especially in Crohn’s disease (CD). Whether switching from intravenous to SC-IFX effectively maintains transmural remission in IBD is still unknown. Methods This is a preliminary report from a prospective multicentre cohort study on IBD patients in clinical and endoscopic remission on IV-IFX treatment switched to SC-IFX. Enrolled patients were followed-up for 12 months, with fecal calprotectin (FC), C-reactive protein (CRP), infliximab trough levels and anti-drug antibodies (ADAs) measured at baseline, at 3, 6 and 12 months. Intestinal ultrasound (IUS) was performed at baseline and every six months. At month 12 a full colonoscopy was performed for mucosal healing assessment. Remission rates and safety profile were subsequently recorded. T-Test and ANOVA for mean comparisons and Kaplan-Meier estimates were used for survival curves. Results 43 IBD patients (69% males) were enrolled, 58% with CD, of whom 52% reported a history of perianal disease. Median disease duration and IFX therapy were 6 (IQR 3-12) and 5 (IQR 2-9) years, respectively. During a median follow-up of 311 (range 122-489) days, clinical remission rate was 98% (Harvey-Bradshaw Index &amp;lt;5 and Mayo score &amp;lt;2). No reactivation of perianal disease was reported. FC and CRP remained stable at each time point (p&amp;gt; 0.05). The median baseline infliximab level was 10.02 ( range 0.1- 41.84) ug/ml. Undetectable infliximab levels (&amp;lt;1 ug/ml) and positive ADAs were found in 6 and 14 patients, respectively; at 3 months, a significant increase in infliximab levels (mean increase 27.5 ng/ml; ± 12.5 SD; p&amp;lt; 0.001) and a progressive decrease of ADAs titer were observed, despite unchanged SC-IFX dose. At baseline, all patients had normal bowel wall thickness (i.e. ileum ≤ 3mm, colon≤4 mm) and a Limberg score ≤1at IUS; reactive lymphadenopathies were reported in 5 patients and a mild abdominal effusion in 1. No significant changes were shown during follow-up. Mild endoscopic activity was found in 2 out 30 patients who performed follow-up endoscopy. Regarding safety profile 12 mild infectious events, 2 mild cutaneous injection site reaction and 1 non-IBD related hospital admission were observed. Conclusion Switching from IV to SC infliximab in a selected cohort of IBD patients confirmed to be safe and effective in maintaining clinical, biochemical, and transmural remission. IUS is a useful, non-invasive and low-cost tool for periodic disease assessment in this subset of patients.

Humoral and cellular immune responses after COVID-19 vaccination of lung transplant recipients and patients on the waiting list: a 6-month follow-up.

Data on cellular response and the decay of antibodies and T cells in time are scarce in lung transplant recipients (LTRs). Additionally, the development and durability of humoral and cellular immune responses have not been investigated in patients on the waitlist for lung transplantation (WLs). Here, we report our 6-month follow-up of humoral and cellular immune responses of LTRs and WLs, compared with controls. Humoral responses to two doses of the mRNA-1273 vaccination were assessed by determining spike (S)-specific IgG antibodies and neutralizing antibodies. Cellular responses were investigated by interferon gamma (IFN-γ) release assay (IGRA) and IFN-γ ELISpot assay at 28 days and 6 months after the second vaccination. In LTRs, the level of antibodies and T-cell responses was significantly lower at 28 days after the second vaccination. Also, WLs had lower antibody titers and lower T-cell responses compared with controls. Six months after the second vaccination, all groups showed a decrease in antibody titers and T-cell responses. In WLs, the rate of decline of neutralizing antibodies and T-cell responses was significantly higher than in controls. Our results show that humoral and cellular responses in LTRs, if they develop, decrease at rates comparable with controls. In contrast, the inferior cellular responses and the rapid decay of both humoral and cellular responses in the WL groups imply that WLs may not be protected adequately by two vaccinations and repeat boostering may be necessary to induce protection that lasts beyond the months immediately post-transplantation.

Persistence of Infectious Human Norovirus in Estuarine Water

Norovirus is the predominant cause of viral acute gastroenteritis globally. While person-to-person is the most reported transmission route, norovirus is also associated with waterborne and foodborne illness, including from the consumption of contaminated bivalve molluscan shellfish. The main cause of shellfish contamination is via the bioaccumulation of norovirus from growing waters impacted by human wastewater. However, data on the persistence of infectious norovirus in the environment are limited due to a lack of a human norovirus culture method in the past. In this study, we applied the recently established method of norovirus replication in human intestinal enteroids to determine the persistence of norovirus in artificial estuarine water at 25 ppt for up to 21 days at 4 °C and 16 °C in the dark. Infectious norovirus was detected for up to 21 days. The relative infectivity declined from 100 to 3% at day 21, with decay rate constants of 0.07 day−1 at 4 °C and 0.17 day−1 at 16 °C. There was no decrease in norovirus titres as measured by reverse transcription-droplet digital PCR (RT-ddPCR), confirming the lack of the relationship between norovirus infectivity and direct detection by PCR. The results confirm that norovirus can remain infectious for at least 3 weeks in an estuarine water environment, presenting associated health risks.

Chemical chaperone TUDCA selectively inhibits production of allergen-specific IgE in a low-dose model of allergy.

The cellular response to endoplasmic reticulum (ER) stress accompanies plasma cell maturation and is one of triggers and cofactors of the local inflammatory response. Chemical chaperones, low-molecular substances that eliminate pathological ER stress, are proposed as means of treating pathologies associated with ER stress. The aim of this study was to evaluate the effect and mechanisms of influence of chemical chaperones on the humoral response in a low-dose model of allergy. The allergic immune response was induced in BALB/c mice by repeated administration of ovalbumin at a dose of 100 ng for 6 weeks. Some animals were injected with both the antigen and the chemical chaperones, TUDCA (tauroursodeoxycholic acid) or 4-PBA (4-phenylbutyrate). Administration of TUDCA, but not 4-PBA, suppressed production of allergen-specific IgE (a 2.5-fold decrease in titer). None of the chemical chaperones affected the production of specific IgG1. The effect of TUDCA was associated with suppression of the switch to IgE synthesis in regional lymph nodes. This phenomenon was associated with suppressed expression of genes encoding cytokines involved in type 2 immune response, especially Il4 and Il9, which in turn could be caused by suppression of IL-33 release. In addition, TUDCA significantly suppressed expression of the cytokine APRIL, and to a lesser extent, BAFF. Thus, TUDCA inhibition of the allergy-specific IgE production is due to suppression of the release of IL-33 and a decrease in the production of type 2 immune response cytokines, as well as suppression of the expression of the cytokines APRIL and BAFF.

МИКРОБИОЛОГИЧЕСКАЯ ОЦЕНКА КОММЕРЧЕСКИХ БИОПРЕПАРАТОВ

The article outlines the results of the total microbial number (PMF), morphological and biochemical analysis of commercial biological products "Bitoxibacillin", "Atlant", "Phytosporin-M" for compliance with manufacturers' descriptions. No pathogenic and conditionally pathogenic microorganisms are found in all studied commercial biological products. The number of cells in 1 g of the product "Phytosporin-M" in both powder and paste form was 2.8 ×109 CFU/g and 3 ×108 CFU/g, respectively, which indicates a higher viability of microorganisms in the powder preparation. In bioproducts with expired shelf life “Bitoxybacillin” and “Atlant” a decrease in cell titer was observed. Bacillus megaterium culture was isolated in the “Atlant” product, whereas Pseudomonas fluorescens, Azotobacter chroococcum, Lactococcus lactis were not detected.

Serological follow-up after syphilis diagnosis in Israel.

The global incidence of syphilis is increasing. Continuity of care challenges the control of sexually transmitted diseases. In this study, we assessed the follow-up and serological decline differences between community- and hospital-diagnosed patients in Israel. A historical cohort study was conducted using the Israel National Syphilis Center (NSC) repository. Patients with a positive non-specific Venereal Disease Research Laboratory (VDRL) test between 2011 and 2020 were included. Rates of serological follow-up and serological titre decreases were compared between hospital- and community-diagnosed patients. The study included 4,445 patients, 2,596 (58.4%) were diagnosed in community clinics and 1,849 (41.6%) in hospitals. Of community-diagnosed patients, 1,957 (75.4%) performed follow-up testing, compared with 834 (51.2%) hospital-diagnosed patients (p<0.001). On multivariate analysis, the odds ratio of serology follow-up among community-diagnosed patients was 2.8 (95 per cent confidence interval (95% CI): 2.2-3.5) that of hospital-diagnosed patients. There were 1,397 (71.4%) community-diagnosed patients with serological titre decrease, compared with 626 (74.9%) hospital-diagnosed patients (p=0.03). On multivariate analysis, this difference diminished. Serological follow-up testing is suboptimal and was performed more often among patients initially diagnosed in the community compared to hospitals. Continuity of care should be improved to promote successful patient care and prevent disease spread.

Neutralizing Antibody Response following a Third Dose of the mRNA-1273 Vaccine among Cancer Patients.

Cancer patients are at an increased risk of morbidity and mortality from SARS-CoV-2 infection and have a decreased immune response to vaccination. We conducted a study measuring both the neutralizing and total antibodies in cancer patients following a third dose of the mRNA-1273 COVID-19 vaccine. Immune responses were measured with an enzyme-linked immunosorbent assay (ELISA) and neutralization assays. Kruskal-Wallis tests were used to evaluate the association between patient characteristics and neutralization geometric mean titers (GMTs), and paired t-tests were used to compare the GMTs between different timepoints. Spearman correlation coefficients were calculated to determine the correlation between total antibody and neutralization GMTs. Among 238 adults diagnosed with cancer, a third dose of mRNA-1273 resulted in a 37-fold increase in neutralization GMT 28 days post-vaccination and maintained a 14.6-fold increase at 6 months. Patients with solid tumors or lymphoid cancer had the highest and lowest neutralization GMTs, respectively, at both 28 days and 6 months post-dose 3. While total antibody GMTs in lymphoid patients continued to increase, other cancer types showed decreases in titers between 28 days and 6 months post-dose 3. A strong correlation (p < 0.001) was found between total antibody and neutralization GMTs. The third dose of mRNA-1273 was able to elicit a robust neutralizing antibody response in cancer patients, which remained for 6 months after administration. Lymphoid cancer patients can benefit most from this third dose, as it was shown to continue to increase total antibody GMTs 6 months after vaccination.

A 4-fold or greater decrease in TPPA titers may indicate effective BPG treatment in primary syphilis

BackgroundIn the majority of clinical environments, the treponema pallidum particle agglutination (TPPA) test is known for its higher specificity compared to the rapid plasma reagin (RPR) test and is commonly employed for the diagnosis of syphilis, but their use for serological monitoring after syphilis therapy is controversial. ObjectivesWe aim to evaluate whether the TPPA titers is suitable for monitoring syphilis treatment efficacy. MethodsAt first, 232 patients with primary syphilis were recruited. Serological testing was performed at baseline (initial visit) and at 6 months (±1 month) after benzathine penicillin G (BPG) treatment. Second, New Zealand white male rabbits were infected with Treponema pallidum (T. pallidum) to evaluate the changes in TPPA titers after BPG therapy. Finally, we compared the TPPA titers in the culture supernatant of rabbit splenocytes stimulated with T. pallidum with or without BPG. ResultsAfter 6 months of treatment, 150 (64.7%) of 232 primary syphilis patients achieved serological cure, and 82 (35.3%) had adverse outcomes. Among 110 patients with TPPA titers decreased by more than fourfold, 109 of them were serological cure patients (≥4-fold decrease in RPR titers) (P ＜ 0.0001). In the rabbit model of syphilis, the TPPA titers was significantly decreased in the treatment subgroup (P = 0.016) and remained constant (±2-fold) or increased (≥4-fold) in the nontreatment subgroup. In addition, T. pallidum resulted in a positive TPPA titers in the culture supernatant of splenocytes (median titers was 1: 80), while BPG could directly reduce the TPPA titers in the culture supernatant (median titers was 1: 40) (P = 0.032). ConclusionsA 4-fold or greater decrease in TPPA titers may indicate effective treatment in primary syphilis. Combining TPPA titers with RPR titers results may potentially aid in the early diagnosis of syphilis.

In Vitro Antiviral Potential of Cucurbitaceae Ecballium elaterium and Its Extract Containing Protease Inhibitors against Bovine Rotavirus

Bovine rotaviruses (BRVs) are significant causative agents of severe diarrhea in newborn calves, resulting in substantial economic losses in the livestock industry. Inhibition of bovine rotavirus using extracts prepared from a Cucurbitaceae plant, which contains trypsin protease inhibitors, might offer a potential anti-rotaviral effect in vitro. Ecballium elaterium (E. elaterium) belongs to the Cucurbitaceae family, indigenous to the Mediterranean, contains E. elaterium trypsin isoinhibitors (EETIso), and has been used in traditional medicine. This study aimed to evaluate the in vitro efficacy of E. elaterium extract against bovine rotavirus infections. Ethanol extracts were prepared from E. elaterium seeds and fruit juice, and their non-toxic concentrations were determined using MA-104 cells. The cells were infected with bovine rotavirus in the presence of E. elaterium extract. The results demonstrated a significant decrease in the rotavirus titer in vitro upon treatment with the E. elaterium extract, suggesting its potential as a therapeutic agent against bovine rotavirus-induced diarrhea in calves. The utilization of E. elaterium extract may contribute to reduced calf mortality, lower medication costs, and improved economic value in cattle farming.

Secondary Syphilis Reinfection with Suspected Asymptomatic Neurosyphilis

Syphilis, a sexually transmitted disease caused by Treponema pallidum, poses a significant global health threat, with an annual incidence of around 12 million cases, predominantly affecting individuals aged 15-49. Reinfection occurs in 11 out of 120 patients, underscoring the importance of effective management. If untreated, 4-9% of cases may progress to early neurosyphilis, often presenting asymptomatically. We present the case of a 22-year-old male with reddish-brown patches on the face, palms, and soles, along with erythematous papules on the genital region, following a history of recent promiscuity. Physical examination revealed distinctive manifestations, including nickels and dimes on the face, syphilitic roseola, Biett's collarette on the palmoplantar region, and erythematous papules-plaques on the scrotal and penile areas. The VDRL test indicated a titer of 1:32, TPHA test &gt;1:5120, and a non-reactive HIV rapid test. Initiating treatment with a single intramuscular injection of benzyl benzathine penicillin G (2.4 million IU) resulted in successful symptom resolution, accompanied by a four-fold decrease in VDRL titer to 1:8 by the third month. However, a subsequent increase to 1:32, following sexual intercourse in the sixth month, indicated reinfection and raised suspicions of asymptomatic neurosyphilis. The patient received oral doxycycline (100 mg twice daily) for 30 days. Unfortunately, treatment success could not be determined as the patient was lost to follow-up. This case report highlights that elevated VDRL titers signify reinfection, treatment failure, or neurosyphilis. Asymptomatic reinfection is common due to lead-time bias and partial immunity, especially with multiple episodes of syphilis. Early neurosyphilis may coexist with primary or secondary syphilis and is frequently asymptomatic. Continued efforts in monitoring and treatment adherence are crucial for effective syphilis management on a global scale.

Comparative study of total antibody titer against SARS-CoV-2 spike protein between male and female COVID- 19 patients of different age groups in UAE

Abstract Introduction/Objective Currently, there is increasing evidence that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes men to experience more serious symptoms and have a higher mortality rate than women, but the associations between gender and age groups are still elusive. This study aimed to examine the associations with age, gender, and clinical parameters of total antibody responses against the spike protein of SARS- CoV-2 after infection in UAE population. Methods/Case Report In this study, spike protein antibody titer estimation for COVID-19 positive individuals (n = 1070) was determined. A cross-sectional study design was planned in which patients were divided into nine groups (based on their age) and further subdivided into two groups based on their genders (9 x 2). Serum was collected from the patients after 17 days of diagnosis as COVID-19 positive by RT-PCR method. Concentrations of SARS-CoV-2 Total antibody (COV2T) were measured by chemiluminescent immunoassay using ADVIA Centaur® XPT systems. We used a mixed effects model to investigate the potential associations of antibodies by bootstrapping t-tests of the putative effects of gender and age of the individuals. Results (if a Case Study enter NA) There were significant differences (P&amp;lt; 0.05) between males and females for SARS-CoV-2 total antibody reactivity. Total 645 (50.4%) male were found reactive compared to 425 (31.2%) female. Noteworthy, the group having middle-aged (41-50 years) participants depicted a higher antibody titer in both males and female against SARS-CoV-2. A significant decrease in titers also observed with different age groups. Highest number of reactive individuals were observed in 41-50 years age group (31%), followed by 31-40 years (27.34%), 51- 60 years (15.21%) and 21-30 years (13.04%). Same pattern of number of reactive individuals was found in male and female of different age group. Moreover, despite there being a weak significant positive association between age and total antibody titre in male patients, while there was no significant correlation between gender and age for the antibody response. Conclusion In a nutshell, total antibody (COV2T) reactivity was found significantly associated with male group and that was highest in 41-50 years age group, irrespective of the gender. These findings are crucial to treat and care for male and female patients infected with COVID-19 at hospitals.

Chinese Severe Hemophilia a Children with High-Titer Inhibitors Obtain More Benefit from Intermediate-Dose Immune Tolerance Induction: The Interim Result of Lome Part a

Background We previously showed that low-dose immune tolerance induction (LD-ITI) strategy [incorporating immunosuppressants (IS) partially] for severe hemophilia A (SHA) patients with high-titer inhibitors (HTI) had relatively equivalent success rate with lower cost compared to those on high-dose ITI from international (I)-ITI randomized clinical trial (RCT). However, it is lack of RCT to compare the efficacy, safety, and cost of LD-ITI strategy to higher-dose ITI [intermediate-dose (MD)-ITI] strategy in China. Currently, the domestic recombinant FVIII (rFVIII) sponsored by the SinoCelltech Ltd., provides an opportunity to conduct the LOME study: a multicenter controlled randomized clinical trial of LOw- versus InterMEdiate-dose immune tolerance induction with recombinant factor VIII in China, to answer this question. Objectives Conduct the RCT to compare the efficacy, safety and cost of LD- to MD-ITI strategy using rFVIII (Omfiloctocog alfa, SCT800) for SHA children with HTI in China. Methods A perspective, multicenter RCT, enrolled SHA children ≤8year-old at enrollment, with peak historical inhibitor-titer 5 - 200 Bethesda Unit (BU)/mL, 1:1 randomized in LD- (Omfiloctocog alfa, rFVIII 50 IU/kg once-every-day) or MD- (Omfiloctocog alfa, rFVIII 100IU/kg/day) ITI group. IS was added (the initial regimen) in patients who met the criteria as follows: (i) the inhibitor titer during ITI increased to ≥200 BU/mL; (ii) the peak titer did not appear within 3 months after ITI-start; (iii) inadequate reduction (&amp;lt;20%) in titer over 6 months. Success: negative inhibitor titer twice consecutively at least 4 weeks apart and FVIII recovery ≥66% of expected within 24 months of treatment. Partial success: negative inhibitor titer twice consecutively at least 4 weeks apart, but with persistently abnormal FVIII recovery. Average consumption cost (per kg body weight) was calculated based on the median number of treatment doses consumed to achieve success. This included the cost of rFVIII and rituximab for ITI, PCC and rFVIIa for treatment of breakthrough bleeding, and IVIG for infection prevention in IS patients. The rituximab and IVIG were calculated based on the actual IS-using rate in 2 groups. Additionally, PCC and rFVIIa were calculated based on the actual using-rate in all breakthrough bleedings. Trial registration number: ChiCTR2200056603. This was the interim analysis. The first participant was enrolled on March 2022. Results Total 31 patients (16 in MD-, 15 in LD-ITI group) from 3 hemophilia centers with median followed-up 9 months since ITI-start (Table 1). A total 26 (83.9%) patients underwent peripherally inserted central catheter (PICC) (14 in MD-, 12 in LD-ITI group). A total 10 (32.3%, 2 in MD-, and 8 in LD-ITI group) patients received IS at median 2.9 months since ITI-start. Among them, 6 patients added IS because of inhibitor titer ≥200BU/mL during ITI, and the rest for delayed-occurred peak-titer or unsatisfactory decrease of titer. The MD- and LD-ITI group achieved similar success rate (75% vs. 40%). None success patients relapsed over a median follow-up period of 5.1 months since achieving success. The Kaplan-Meier curves demonstrated that patients in MD-ITI group had significantly shorter time to success (median, 2.9 months vs. 9.0 months), and partial success (2.4 months vs. 5.7 months). (Figure 1A and Figure 1B) Patients in MD-ITI group had lower mean bleeding rate (bleedings/month) (0.38 vs. 1.40) and joint bleeding rate (0.11 vs. 0.83) before achieving partial success, compared with those in LD-ITI group (Figure 1C and Figure 1D). But during the phase from achieving partial success to achieving success, the 2 groups had similar bleeding rate (0.09 vs. 0.11) and joint bleeding rate (0.07 vs. 0.16). A total 6 (23.1%) patients occurred PICC-related complications (5 in MD-, 1 in LD-ITI group) with mean follow-up period of 270 days. All complications including infection (1 person-time), thrombosis (1 person-time), rashes (3 person-time), accidental detachment (3 person-time). Similar per kg treatment cost from ITI-start to ITI success was found in 2 groups (US$ 2905.18 vs. US$ 2838.23). Conclusions Similar success rate was found in LD-ITI (rFVIII) strategy and MD-ITI (rFVIII) strategy for SHA children with HTI. On the premise of similar cost, shorter time to success, less bleedings were observed in MD-ITI strategy. PICC implantation is a safe option to conduct ITI.

Persistence of SARS-CoV-2-antibodies against N, S and RBD after natural infection.

Coronavirus disease 2019 (COVID-19) pandemic has affected most countries in the world. Monitoring the humoral immune responses during the natural course of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection and the duration of them provide useful information for the development of vaccination strategies against this virus and its emerging variants. The importance of the antibody response especially neutralizing antibodies in long-term immunity to SARS-CoV-2 is significant. The present study is a cross-sectional study of sero-epidemiological type that has been proposed to compare the persistence of Immunoglobulin G (IgG) against N (nucleocapsid), S (spike) and RBD (receptor-binding domain) proteins in the community after the time of primary disease. A total of 652 serum samples were collected from hospital staff working in COVID wards, as well as a number of community members with different occupations, among those with positive antibody titers, 86 participated in the resampling test before vaccination. There was no association between antibody titer and disease severity (p>0.05). A significant decrease in Ab levels was observed in the paired second samples. The highest rate of decrease was related to anti-N, then anti-RBD and anti-S IgG levels, respectively. There is a significant relationship between the initial antibody titer and its reduction over time (p-value <0.05). Our data revealed that humoral immunity following natural infection of SARS-CoV-2 is detectable for at least 4 months, regardless of disease severity. The most decrease in antibody titer over time was related to anti-N IgG levels.