High Risk Of Opportunistic Infections Research Articles

Evaluation of the effects of Artemisia Annua L. and Moringa Oleifera Lam. on CD4 count and viral load among PLWH on ART at Mbarara Regional Referral Hospital: a double-blind randomized controlled clinical trial

BackgroundInitiation of ART among people living with HIV (PLWH) having a CD4 count ≤ 350cells/µl, produces poor immunological recovery, putting them at a high risk of opportunistic infections. To mitigate this, PLWH on ART in Uganda frequently use herbal remedies like Artemisia annua and Moringa oleifera, but their clinical benefits and potential antiretroviral (ARV) interactions remain unknown. This study examined the impact of A. annua and M. oleifera on CD4 count, viral load, and potential ARV interactions among PLWH on ART at an HIV clinic in Uganda.Methods282 HIV-positive participants on antiretroviral therapy (ART) with a CD4 count ≤ 350cells/µl were randomized in a double-blind clinical trial to receive daily, in addition to their routine standard of care either; 1) A. annua leaf powder, 2) A. annua plus M. oleifera, and 3) routine standard of care only. Change in the CD4 count at 12 months was our primary outcome. Secondary outcomes included changes in viral load, complete blood count, and ARV plasma levels. Participants were followed up for a year and outcomes were measured at baseline, 6 and 12 months.ResultsAt 12 months of patient follow-up, in addition to standard of care, administration of A. annua + M. oleifera resulted in an absolute mean CD4 increment of 105.06 cells/µl, (p < 0.001), while administration of A. annua plus routine standard of care registered an absolute mean CD4 increment of 60.84 cells/µl, (p = 0.001) compared to the control group. The A. annua plus M. oleifera treatment significantly reduced viral load (p = 0.022) and increased platelet count (p = 0.025) and white blood cell counts (p = 0.003) compared to standard care alone, with no significant difference in ARV plasma levels across the groups.ConclusionA combination of A. annua and M. oleifera leaf powders taken once a day together with the routine standard of care produced a significant increase in CD4 count, WBCs, platelets, and viral load suppression among individuals on ART. A. annua and M. oleifera have potential to offer an affordable alternative remedy for managing HIV infection, particularly in low-resource communities lacking ART access.Trial registrationClinicalTrials.gov NCT03366922.

Diagnosis of TB Granuloma in SLE Patient by Kidney Biopsy

Lupus Nephritis is a common clinical manifestation affecting more than 50% of patients with Systemic Lupus Erythematosus (SLE), a chronic autoimmune disease that can affect virtually any organ. Whilst lupus nephritis is typically detected by an abnormal urinalysis with or without an elevated plasma creatinine, diagnosis is confirmed on renal biopsy. It is characterized by immunologic abnormalities including formation of immunocomplex deposits affecting the glomerular basement membrane, mesangium and/or subendothelial. It is by nature an immunocompromised state and along with its immunosuppressive treatment, lupus nephritis places a patient at high risk of opportunistic infections, including Tuberculosis (TB). A 21-year-old female presented with clinical features suggestive of lupus nephritis and a preserved renal function. The diagnosis was later confirmed on renal biopsy with an incidental finding of TB on renal histopathology. Interestingly, the patient had no constitutional symptoms or clinical history suggestive of TB. Antituberculosis treatment was initiated and mycophenolate, enalapril and prednisone was boarded after 2 weeks of TB treatment. The patient was later lost to follow up due to defaulting chronic treatment and follow up.

Religious and traditional beliefs and practices as predictors of mental and physical health outcomes and the role of religious affiliation in health outcomes and risk taking

BackgroundWhile many studies from sub-Saharan countries, including Zimbabwe, allude to the important role of religion and tradition for young people living with HIV (YPLHIV), most of these studies tend to be descriptive and lack advanced statistical analysis. This study aims to close this gap.MethodsData for this study was collected between July and October 2021 from 804 YPLHIV (aged 14–24) in Zimbabwe. The questionnaire included questions regarding participants’ conceptions of HIV, their health seeking and risk-taking behaviour, current HIV viral load results, the prevalence of opportunistic infections, their mental health status, and demographic characteristics. The analysis was done using multilevel mixed-effects logistic regression.ResultsWe found that Traditional religious affiliation was linked to overall lower viral load (OR: 0.34; CI: 0.12–0.96; P: 0.042), Apostolic to more (OR: 1.52; CI: 1-2.3; P: 0.049) and Pentecostal to less (OR: 0.53; CI: 0.32–0.95; P: 0.033) treatment failure. Additionally, conceptions about HIV without spiritual or religious connotation, such as ‘seeing HIV as result of a weak body’ was associated with lower risk of treatment failure (OR: 0.6; CI: 0.4-1.0; P: 0.063), higher chances for undetectable viral load (OR: 1.4; CI: 1–2; P: 0.061), and overall lower viral load (OR: 0.7; CI: 0.5-1; P: 0.067). Moralizing concepts of HIV, like ‘seeing HIV as a result of sin in the family’, was linked to higher risk of opportunistic infections (OR:1.8; CI:1.1-3; P: 0.018), and higher risk of treatment failure (OR: 1.7; CI: 0.7–1.1; P: 0.066). Religious objections toward certain forms of therapy, like toward cervical cancer screening, was linked to higher risk of mental problems (OR: 2.2; CI: 1.35–3.68; P: 0.002) and higher risk of opportunistic infections (OR:1.6; CI:1.1–2.1; P: 0.008). Religious affiliations significantly influenced conceptions of HIV, health seeking behaviour, and risk taking.ConclusionTo our knowledge, this study is the first to provide evidence about the statistically significant associations between religious and traditional beliefs and practices and current health outcomes and health risk factors of YPLHIV in Zimbabwe. It is also the first to identify empirically the role of religious affiliations as predictors of current viral load results. This new knowledge can inform contextualized approaches to support YPLHIV in Zimbabwe.

Impact of an Intervention to Promote the Vaccination of Patients with Inflammatory Bowel Disease.

Patients with inflammatory bowel disease (IBD) have a dysregulated immune system, being at high risk of opportunistic infections. Low vaccination rates hinder the prevention of such diseases. Therefore, we implemented an intervention to increase vaccination rates, and we aimed to evaluate the effect. We determined the change in professionals and the change in the vaccination rates after the intervention. A quasi-experimental study was carried out using data from 31 December 2016 to 31 December 2021. First, healthcare professionals specializing in IBD agreed on a vaccination protocol; then, this protocol was passed on to the professionals involved in vaccination. We evaluated the perception of knowledge, capacity, and intention to vaccinate patients with IBD among the professionals before and after the intervention with a survey. We also described the effectiveness of the intervention for already diagnosed patients and compared the vaccination rates between patients diagnosed prior to the intervention and newly diagnosed patients. The intervention resulted in an improved perception of knowledge, capacity, and intention to vaccinate patients with IBD among the professionals (p < 0.05). Moreover, during the post-intervention period, in the 315 patients, the vaccination rate increased for all immune-preventable diseases (p < 0.05). The professionals positively valued the intervention, and compliance with the recommended vaccination protocol in patients with IBD improved significantly.

Prevalence of Histoplasma Antigenuria among Outpatient Cohort with Advanced HIV in Kampala, Uganda.

In sub-Saharan Africa, an estimated 25% of people with HIV present with advanced HIV and are at high risk of opportunistic infections. Whereas histoplasmosis has occasionally been seen in Uganda, the understanding of the local risk of acute infection is limited. We sought to determine the prevalence of Histoplasma antigenuria using an enzyme immunoassay (EIA, clarus Histoplasma GM EIA, IMMY; Norman, OK, USA) in a cohort of outpatients with advanced HIV disease in Kampala, Uganda. Among the persons with positive urine Histoplasma antigen tests, we assessed their clinical presentation and outcomes. The EIA was run on stored urine samples as per the manufacturer's instructions. Specimens ≥1 EIA units were considered positive. Among the 388 tested urine samples, 4 (1.2%) were positive for Histoplasma antigen. The histoplasmosis prevalence among participants with a CD4 < 100 cells/mcL was 2.5% (4/158). Three of the four participants with a positive Histoplasma antigen test reported systemic symptoms consistent with histoplasmosis. All four participants had a positive urine lipoarabinomannan test and were treated for tuberculosis. By the four-week follow-up visit, all participants were clinically improved, alive, and in care without antifungal therapy. In advanced HIV, the clinical presentations of tuberculosis and histoplasmosis overlap. The value of histoplasmosis screening and pre-emptive treatment is an area of future research.

Effect of COVID-19 on Myasthenia Gravis (P2-8.006)

<h3>Objective:</h3> To describe the effects of COVID-19 on comorbid myasthenia gravis (MG) regarding common symptoms such as limb weakness, oculobulbar weakness, and respiratory failure by evaluating worsening MGFA scores or therapy escalation following COVID-19 infection. <h3>Background:</h3> Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by fluctuating weakness that affects the limbs, oculobulbar muscles, and diaphragm. Therapies include steroids and immunosuppressants, placing patients at high risk of opportunistic infections. Certain triggers can worsen MG, such as medications and infections. We describe the outcomes of 36 patients with confirmed MG and COVID-19, with particular focus on changes in Myasthenia Gravis Foundation of America (MGFA) scores and treatment escalation following infection. <h3>Design/Methods:</h3> Single center retrospective chart review of 36 patients from March 2020-January 2022 with clinically or serologically confirmed MG and COVID-19 <h3>Results:</h3> Of these 36 patients, 20 (55.6%) were not vaccinated against COVID. Twelve patients (33%) had MGFA scores of 3 or 4. Nineteen patients (53%) were prescribed steroids and 18 patients (50%) were on alternate immunotherapy prior to diagnosis of COVID. A total of 5 patients (14%) had a change in baseline MGFA score. One patient’s MGFA score worsened from 1 to 2 and 4 patients required MG treatment escalation. <h3>Conclusions:</h3> Myasthenia gravis patients with higher premorbid MGFA scores, steroid use, or other immunosuppressive therapy would be expected to have worse clinical outcomes in their MG course following COVID infection. Our results indicate 14% of MG patients with COVID had a change from their baseline MGFA score. Our study results revealed higher premorbid MGFA scores or use of immunosuppressant therapy did not alter a patient’s MGFA score following COVID infection. These results are consistent with current literature that COVID infection has little impact on these patients. <b>Disclosure:</b> Dr. Sandhu has nothing to disclose. Dr. Quezada has nothing to disclose. Dr. Rana has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CSI. Dr. Rana has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pharmawrite. Dr. Rana has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven. Dr. Rana has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Argenx. Dr. Rana has received personal compensation in the range of $500-$4,999 for serving as a Consultant for amylyx. Dr. Rana has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Small has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion.

Advanced HIV disease: A review of diagnostic and prophylactic strategies.

Despite expanded access to antiretroviral therapy (ART) and the rollout of the World Health Organization's (WHO) 'test-and-treat' strategy, the proportion of people with HIV (PWH) presenting with advanced HIV disease (AHD) remains unchanged at approximately 30%. Fifty percent of persons with AHD report prior engagement to care. ART failure and insufficient retention in HIV care are major causes of AHD. People living with AHD are at high risk for opportunistic infections and death. In 2017, the WHO published guidelines for the management of AHD that included a comprehensive package of care for screening and prophylaxis of major opportunistic infections (OIs). In the interim, ART regimens have evolved: integrase inhibitors are first-line therapy globally, and the diagnostic landscape is evolving. The objective of this review is to highlight novel point-of-care (POC) diagnostics and treatment strategies that can facilitate OI screening and prophylaxis for persons with AHD. We reviewed the WHO guidelines for recommendations for persons with AHD. We summarized the scientific literature on current and emerging diagnostics, along with emerging treatment strategies for persons with AHD. We also highlight the key research and implementation gaps together with potential solutions. While POC CD4 testing is being rolled out in order to identify persons with AHD, this alone is insufficient; implementation of the Visitect CD4 platform has been challenging given operational and test interpretation issues. Numerous non-sputum POC TB diagnostics are being evaluated, many with limited sensitivity. Though imperfect, these tests are designed to provide rapid results (within hours) and are relatively affordable for resource-poor settings. While novel POC diagnostics are being developed for cryptococcal infection, histoplasmosis and talaromycosis, implementation science studies are urgently needed to understand the clinical benefit of these tests in the routine care. Despite progress with HIV treatment and prevention, a persistent 20%-30% of PWH present to care with AHD. Unfortunately, these persons with AHD continue to carry the burden of HIV-related morbidity and mortality. Investment in the development of additional POC or near-bedside CD4 platforms is urgently needed. Implementation of POC diagnostics theoretically could improve HIV retention in care and thereby reduce mortality by overcoming delays in laboratory testing and providing patients and healthcare workers with timely same-day results. However, in real-world scenarios, people with AHD have multiple comorbidities and imperfect follow-up. Pragmatic clinical trials are needed to understand whether these POC diagnostics can facilitate timely diagnosis and treatment, thereby improving clinical outcomes such as HIV retention in care.

Toxoplasma gondii, HBV, and HCV co‐infection and their correlation with CD4 cells among Iranian HIV‐positive patients

Human immunodeficiency virus (HIV/AIDS) infected patients have a higher risk of opportunistic infections (OIs) depending on their immunological status, especially CD4 + cell count. Toxoplasma gondii, hepatitis C virus (HCV), and hepatitis B virus (HBV) are important OIs among Human Immunodeficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDS) patients. However, little is known about co-infection of these pathogens among HIV-infected individuals and their correlation with the patient's CD4 + cell count. Hence, this study aimed to investigate the serological and molecular status of T. gondii infection among HIV-infected individuals who had co-infection with HBV and HCV infections. A total of 100 HIV/AIDS patients in two cities in the southwest of Iran was tested for T. gondii Immunoglobulin G (IgG) and Immunoglobulin M (IgM) antibodies as well as DNA detection by polymerase chain reaction (PCR) targeting the RE gene. HBV and HCV were detected by hepatitis B surface antigen (HBsAg) test, hepatitis C antibody (HCV Ab) test, and Real-Time PCR. The number of CD4 + cell counts was determined by Flow cytometry. Anti-T. gondii IgG was positive in 22% of the patients, but anti-T. gondii IgM and PCR were negative in all samples. HBV and HCV were positive in 8% and 33% of the patients, respectively. Co-infections were as followed: HIV + HCV (16%), HIV + HCV + T. gondii (11%), HIV + T. gondii (5%), HIV + HBV (1%), HIV + HBV + T. gondii (1%), HIV + HBV + HCV (1%), and HIV + HBV + HCV + T. gondii (5%). A significant decline in CD4 + cell counts was found in such co-infection groups (HIV + T. gondii, HIV + HCV + T. gondii, and HIV + HBV + HCV + T. gondii) compared with the HIV mono-infection group. Our study showed that co-infections of T. gondii, HCV, and HBV were common among HIV-infected patients and co-infections had a negative correlation with CD4 + cell counts of the patients.

New immunosuppressive agents in transplantation

Immunosuppressive agents have enabled the development of allogenic transplantation during the last 40 years, allowing considerable improvement in graft survival. However, several issues remain such as the nephrotoxicity of calcineurin inhibitors, the cornerstone of immunosuppressive regimens and/or the higher risk of opportunistic infections and cancers. Most immunosuppressive agents target T cell activation and may not be efficient enough to prevent allo-immunization in the long term. Finally, antibody mediated rejection due to donor specific antibodies strongly affects allograft survival.Many drugs have been tested in the last decades, but very few have come to clinical use. The most recent one is CTLA4-Ig (belatacept), a costimulation blockade molecule that targets the second signal of T cell activation and is associated with a better long term kidney function than calcineurin inhibitors, despite an increased risk of acute cellular rejection.The research of new maintenance long-term immunosuppressive agents focuses on costimulation blockade. Agents inhibiting CD40-CD40 ligand interaction may enable a good control of both T cells and B cells responses. Anti-CD28 antibodies may promote regulatory T cells. Agents targeting this costimulation pathways are currently evaluated in clinical trials.Immunosuppressive agents for ABMR treatment are scarce since anti-CD20 agent rituximab and proteasome inhibitor bortezomib have failed to demonstrate an interest in ABMR. New drugs focusing on antibodies removal (imlifidase), B cell and plasmablasts (anti-IL-6/IL-6R, anti-CD38…) and complement inhibition are in the pipeline, with the challenge of their evaluation in such a heterogeneous pathology.

Rhizomucor pusillus Infection in a Patient with Acute Myeloid Leukaemia After Haematopoietic Stem Cell Transplantation: Clinical Impact of Metagenomics Next-Generation Sequencing

Long-term chemotherapy and immunosuppressants in acute myeloid leukaemia (AML) patients can result in a high risk of opportunistic infections. Rhizomucor pusillus is an opportunistic pathogen that exists in nature, but infection caused by R. pusillus is rare in the clinic. Notably, the sensitivity and detection time of conventional diagnostic tools for this fungus usually falls short of the needs of clinical diagnosis, resulting in treatment failure. Currently, metagenomics next-generation sequencing (mNGS) has played an important role in the detection of pathogens. Here, we report a case of R. pusillus pneumonia in a haematopoietic stem cell transplantation (HSCT) patient, detected by the mNGS method.

Prescribing Pattern of Antibiotics in Respiratory Tract Infections in the Pediatric Indoor Patients at Manipal Teaching Hospital

Introduction: Respiratory tract infections are the most frequently occurring illness in childhood and antibiotics are the key drugs for its treatment which account for three-quarters of all antibiotics prescriptions. Injudicious use of antibiotics leads to the development of resistance, patients are at high risk for opportunistic infections or prolonged hospitalization. This study aimed to assess the prescribing pattern of antibiotics for respiratory tract infections in the pediatric indoor patients of Manipal Teaching Hospital.&#x0D; Methods: This study is a prospective cross-sectional study done in the paediatrics ward of Manipal Teaching Hospital Pokhara, conducted for six months. Patients aged range from 1 day to 14 years who meet the inclusion criteria were taken in this study. Data were collected from the inpatient ward and analysed using various statistical tools.&#x0D; Results: Among 170 patients, a maximum(43.3%) were in the age group of 1 day to 11 months with male predominance(74.1%). Bronchopneumonia was the most common respiratory tract infection (51.8%) followed by bronchiolitis (13%). Chest x-ray was done in all patients however blood culture was done only in 60.6% and an antibiotic sensitivity test (27.6%) before prescribing antibiotics. Cefotaxime was prescribed in maximum patients (62.4%) followed by ceftriaxone (17.1%). All the patients received at least one antibiotic by i.v route during the hospital stay.&#x0D; Conclusion: Since culture and sensitivity tests were not carried out on most of the patients before prescribing antibiotics in this study, which might lead to an increased chance of bacterial resistance and treatment failure in the future.

Immunogenic and immunotolerogenic effects of extracorporeal photopheresis in high immunological risk kidney recipients. A single center case series

The immunomodulatory effects of extracorporeal photopheresis (ECP) have been used for the treatment of T-cell mediated disorders, such as rejection in organ transplantation. Currently, it is an established therapy for heart and lung rejection, but not for kidney transplantation (KT), where experience is limited. In addition, some data suggest that ECP could generate an immune response against infections, thus being an alternative for the treatment of rejection in case of active or high-risk of infection. In the present study, we analyze four cases of use of ECP as concomitant therapy in patients with KT and high risk of opportunistic infections due to the high burden of immunosuppression throughout their renal diseases. Two patients had concomitant viral infection (cytomegalovirus and BK virus, respectively) and three patients were on treatment for graft rejection. In the two patients with active viral infection, the infection was successfully controlled during ECP treatment. In all cases, ECP has been shown to be a safe procedure, without complications.

Левилимаб в лечении COVID-19

Levilimab, a monoclonal antibody interacting with soluble and mebrane bound IL-6 receptors, was recently approved in Russia for the treatment of acute respiratory distress syndrome in COVID-19 patients. Efficacy and favorable safety profile of levilimab were shown in the randomised doubleblind placebo controlled CORONA trial in 206 patients with COVID-19 associated pneumonia, who had at least one criteria of the disease severity, that is, increased respiration rate, reduced SpO2 (≤93%) or PaO2 /FiO2 (≤300 mm Hg), progressive lung disease, etc. The primary end-point of this study was the percentage of patients with stable improvement by ordinal scale (without a need in rescue levilimab injection) at day 14. Stable improvement was achieved in 63.1% and 42.7% of patients in the levilimab and placebo groups, respectively (р=0.0017), and this difference was consistent at the end of 30-day follow-up. Analysis of various secondary end-points, such as a need in rescue open-label levilimab or admission to ICU, confirmed efficacy of IL-6 inhibitor in patients with COVID -19. IL-6 inhibition was not associated with a higher risk of opportunistic infections. The authors present the case of successful levilimab administration in hospitalized patient with hypoxia and systemic inflammation and discuss the practical issues of IL-6 inhibitors use in COVID-19 patients.

High incidence and mortality of Pneumocystis jirovecii infection in anti-MDA5-antibody-positive dermatomyositis: experience from a single center

BackgroundIdiopathic inflammatory myopathies (IIM) are associated with a significantly higher risk of opportunistic infections including Pneumocystis jirovecii pneumonia (PJP), a potentially fatal opportunistic infection. However, no prior studies have evaluated PJP infection in subtypes of IIM.ObjectivesTo investigate the prevalence and mortality rate of PJP infection in subgroups of IIM patients stratified according to myopathy-specific antibodies.MethodsIn the first part of the study, 463 consecutive patients with IIM were prospectively followed for a period of at least 1 year to analyze the incidence of PJP. In the second part of the study, we enrolled 30 consecutive PJP patients with any rheumatic disease in order to identify the mortality rate and risk factors by Cox regression analysis. The Kaplan-Meier method with log-rank testing was used to assess differences in survival.ResultsThe prevalence of PJP in IIM patients was found to be 3.0/100 person-years, while in MDA5+ DM patients it was 7.5/100 person-years and in MDA5− IIM patients 0.7/100 person-years (P < 0.05). PJP typically occurred in the first 2 months in the case of MDA5+ DM patients who had a significant decrease in their CD4+ T cell counts and lymphocyte counts (P < 0.05). In PJP patients, 3-month mortality was higher for MDA5+ DM patients than in those with other rheumatic diseases (83.3% vs 38.9%, P < 0.05). Alarmingly, MDA5+ DM patients seemed not to benefit from prompt anti-PJP treatment, unlike patients with other rheumatic diseases whose survival improved when anti-PJP treatment was started within 6 days (P < 0.05).ConclusionPJP has an alarming high incidence and mortality in MDA5+ DM patients. Timely treatment for PJP seems not to improve the prognosis of patients with this particular subtype. Hence, there remains a crucial unmet need to develop PJP prophylaxis for MDA5+ DM patients.

A high concentration of TGF-β correlates with opportunistic infection in liver and kidney transplantation

Transforming growth factor-β (TGF-β) has been associated with numerous human infections, but its role in the occurrence of opportunistic infection (OI) after solid organ transplantation remains unexplored. This study aimed to assess the utility of the TGF-β following in vitro stimulation of whole peripheral blood (WPB) as a surrogate biomarker of post-transplant OI in a cohort of liver and kidney recipients.Thirty liver and thirty-one kidney transplant recipients were recruited to be prospectively monitored for one-year post-transplantation. Enzyme-linked immunosorbent assay (ELISA) was performed to calculate IFN-γ, IL-17, IL-10 and TGF-β concentration in the supernatant from the activated WPB.Recipients showed higher TGF-β concentrations compared to IFN-γ, IL-17, IL-10 at baseline, although these differences were not significant between INF and NoINF. However, recipients who developed an OI within the first sixth months had a higher concentration of TGF-β than those without OI. A concentration of TGF-β > 363.25 pg/ml in liver and TGF-β > 808.51 pg/ml in kidney recipients were able to stratify patients at high risk of OI with a sensitivity and specificity above 70% in both types of solid organ transplantations.TGF-β could provide valuable information for the management of liver and kidney recipients at risk of post-transplant infection.

Thymic Engraftment by in vitro-Derived Progenitor T Cells in Young and Aged Mice.

T cells play a critical role in mediating antigen-specific and long-term immunity against viral and bacterial pathogens, and their development relies on the highly specialized thymic microenvironment. T cell immunodeficiency can be acquired in the form of inborn errors, or can result from perturbations to the thymus due to aging or irradiation/chemotherapy required for cancer treatment. Hematopoietic stem cell transplant (HSCT) from compatible donors is a cornerstone for the treatment of hematological malignancies and immunodeficiency. Although it can restore a functional immune system, profound impairments exist in recovery of the T cell compartment. T cells remain absent or low in number for many months after HSCT, depending on a variety of factors including the age of the recipient. While younger patients have a shorter refractory period, the prolonged T cell recovery observed in older patients can lead to a higher risk of opportunistic infections and increased predisposition to relapse. Thus, strategies for enhancing T cell recovery in aged individuals are needed to counter thymic damage induced by radiation and chemotherapy toxicities, in addition to naturally occurring age-related thymic involution. Preclinical results have shown that robust and rapid long-term thymic reconstitution can be achieved when progenitor T cells, generated in vitro from HSCs, are co-administered during HSCT. Progenitor T cells appear to rely on lymphostromal crosstalk via receptor activator of NF-κB (RANK) and RANK-ligand (RANKL) interactions, creating chemokine-rich niches within the cortex and medulla that likely favor the recruitment of bone marrow-derived thymus seeding progenitors. Here, we employed preclinical mouse models to demonstrate that in vitro-generated progenitor T cells can effectively engraft involuted aged thymuses, which could potentially improve T cell recovery. The utility of progenitor T cells for aged recipients positions them as a promising cellular therapy for immune recovery and intrathymic repair following irradiation and chemotherapy, even in a post-involution thymus.

The Efficiency of the Fight Against HIV, in Constanta, from the Perspective of Neurological Complications

Abstract In order to control and end the AIDS epidemic, we all need to hit the 0-0-0 target. That means 0 HIV infections, 0 mortality caused by AIDS and 0 discrimination. We performed a retrospective observational analytical study on 166 HIV positive patients with a neurological complication, diagnosed between June 2012 and June 2020, in Clinical Infectious Diseases Hospital of Constanta. We collected data from the observational charts that revealed if the patient was known with HIV infection at the time of the neurological complication diagnosis, information about the treatment (how many treatment regimens, classes of antiretroviral drugs, CNS Penetration-Effectiveness Rank), treatment compliance. The patients were divided into two groups: first group “opportunistic infections (OI)” and second group “other neurological conditions (ONC)”. 16 patients (9,6%) have the neurological condition as first manifestation of HIV infection. Opportunistic infections, correlated with a poor immunological status continue to have a high percentage (46,98%) of neurological complications, being associated with a poor treatment compliance (p&lt;0,001). Integrase inhibitors were associated, in this study, more with opportunistic infections and less with other neurological conditions (OR=2,885; 95% IC), this finding needs further research. Long term survivors have problems with treatment compliance manifesting treatment fatigue, even if they have treatment regimens with good CNS penetrability. Poor compliance is associated with high risk of opportunistic infections and opportunistic infections have a higher mortality than other neurological complications. Our task for the future is to find ways to improve treatment adherence in order for HIV patients to have a better and longer life.

Isolated central nervous system Aspergillosis infection in a chronic lymphocytic leukemia patient on Ibrutinib: A case report

BackgroundIn patients at high risk of opportunistic infections who present with isolated.neurological symptoms, it is lifesaving to consider Central Nervous System Aspergillosis (CNS-A). Ibrutinib use in chronic lymphocytic leukemia (CLL) has previously been associated with CNS-A. We provide a case report of a patient that presented with primary CNS-A on Ibrutinib therapy without any prior pulmonary or local paranasal signs of infection.Case presentation74-year-old Caucasian male with CLL and no prior chemotherapy on ibrutinib for 6 months presented with three months of unsteady gait, occipital headache, and confusion. He has a history of pulmonary sarcoidosis on chronic prednisone 5 mg daily and chronic obstructive pulmonary disease (COPD). He was found to have a “brain abscess” on imaging. Emergent craniotomy confirmed Aspergillus and patient was treated with Voriconazole for 6 months. At six-month follow up, repeat magnetic resonance imaging (MRI) confirmed complete resolution of CNS lesion.ConclusionsOur case reinforces the importance of being vigilant for isolated CNS-A in CLL patients on ibrutinib who present with neurological symptoms and signs, without prior or co-infection of sino-pulmonary tissue.

Vitis Vinifera L.: A new bioactive anticandidal agent to combat oral candidal carriage in Down syndrome patients.

Down syndrome (DS) patients have a high risk of opportunistic infections from Candida species. Therefore, the purpose of this research was to assess the prevalence of Candida species in oral cavity of DS patients and investigating of grape seed extract (GSE) as a potential anticandidal agent. Our study included fifty patients with DS and fifty healthy children. Oral tongue swabs were taken from both groups and isolated Candida species were identified. The anticandidal activity of GSE against isolated Candida was studied using agar well diffusion method. Scanning electron microscope (SEM) was used to determine the major alterations in Candida after GSE treatment. GSE was subjected to GC-MS analysis and HPLC analysis. Forty six samples showed growth of Candida in DS group, where as ten samples in control group. The most common pathogenic Candida isolated from DS patients was C.tropicalis (65.2%). GSE showed significant inhibitory activity against C.tropicalis (MIC 30 mg/ml). The SEM showed complete alterations in Candida cell morphology. GC-MS chromatogram of GSE revealed 30 compounds, the major one is (9, 12-Octadecadienoic acid) which confirmed by HPLC chromatogram with a peak at RT 20.311 min. GSE could be a promising anticandidal agent and it may form a primary platform for further toxicological assessment and development of new drugs.

A case report of central nervous system mucormycosis and aspergillus pneumopericardium in a renal transplant recipient

Renal transplant recipients are at high risk of opportunistic infections. The occurrence of infections is influenced by the intensity of immunosuppression, microbial exposures and other environmental and systemic factors. We present a case of a postrenal transplant recipient who developed polymicrobial infections, including bacterial and invasive fungal infections involving the cerebrum (Mucormycosis) and lung (Aspergillosis) complicated by extension into the pericardial cavity. Despite treatment with intravenous antibiotics and antifungals along with surgical debridement of infective focus, the patient succumbed to the illness. Fungal infections in posttransplant population can have myriad presentations and many pathogens can become locally and systemically invasive unless detected and controlled in a timely manner. Risk factors such as hyperglycemia and high immunosuppression should be appropriately addressed for the prevention of high-grade infections.