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Experimental and Clinical... Oct 2023A common complication after transplant is an opportunistic infection, in part due to the necessary immunosuppression regimens that patients are placed on. This study...
OBJECTIVES
A common complication after transplant is an opportunistic infection, in part due to the necessary immunosuppression regimens that patients are placed on. This study aimed to assess the outcomes and rates of infection in kidney transplant recipients on belatacept compared with kidney transplant recipients on standard immunosuppression therapy.
MATERIALS AND METHODS
We conducted a matched-pair case-control retrospective analysis of a prospectively recollected database of all adult kidney transplant patients at the SUNY Upstate Medical Hospital from January 1, 2016, to July 31, 2022.
RESULTS
Among study patients, 60.5% of patients in the belatacept group and 47.9% of patients in the standard immunosuppression regimen group were diagnosed with an infectious disease during follow-up, although no significant difference was shown between the 2 groups (P = .21). The most common infection in both groups was urinary tract infection, which was comparable between the groups (41.8% vs 50%; P = .42). No significant difference was shown between patients with early and late conversion to belatacept in terms of infection incident and type.
CONCLUSIONS
Kidney transplant recipients who were converted to belatacept because of poor renal function had a similar infection rate compared with patients on standard immunosuppression treatment. Neither conversion to belatacept nor timing of conversion changed the risk of infection after kidney transplant. Our findings suggest that physicians may convert a kidney transplant recipient with poor renal function to belatacept without changing the patient's risk of opportunistic infection.
Topics: Adult; Humans; Abatacept; Kidney Transplantation; Immunosuppressive Agents; Calcineurin Inhibitors; Retrospective Studies; Graft Rejection; Graft Survival; Opportunistic Infections; Transplant Recipients
PubMed: 37965954
DOI: 10.6002/ect.2023.0137 -
ARP Rheumatology 2023Cytomegalovirus (CMV) infection is a common and typically benign disease in immunocompetent individuals. However, immunocompromised patients are at a greater risk of...
Cytomegalovirus (CMV) infection is a common and typically benign disease in immunocompetent individuals. However, immunocompromised patients are at a greater risk of reactivation, leading to more severe outcomes. Patients with rheumatic diseases have a particularly high risk of opportunistic infections due to both the inherent immunosuppressive state conveyed by the disease itself and the use of potent immunosuppressant drugs, such as glucocorticoids, cyclophosphamide, and rituximab. Limited data are available regarding prophylactic or preemptive treatment of CMV infection in patients with rheumatic diseases. In this article the authors present two cases of rheumatic conditions complicated by CMV infection. The first case describes a patient with eosinophilic granulomatosis with polyangiitis, previously treated with glucocorticoids and cyclophosphamide, who developed CMV colitis with bowel perforation. The second case involves a woman with systemic lupus erythematosus who was diagnosed with CMV meningitis. Both cases reinforce the importance of establishing guidelines for surveillance and prophylaxis of CMV infection in these patients.
Topics: Female; Humans; Churg-Strauss Syndrome; Cyclophosphamide; Cytomegalovirus; Cytomegalovirus Infections; Glucocorticoids; Granulomatosis with Polyangiitis; Immunosuppressive Agents; Opportunistic Infections; Rheumatic Diseases
PubMed: 37839034
DOI: No ID Found -
Current Hematologic Malignancy Reports Apr 2020CMV DNA polymerase inhibitors such as ganciclovir and foscarnet have dramatically reduced the burden of CMV infection in the HCT recipient. However, their use is often... (Review)
Review
PURPOSE OF REVIEW
CMV DNA polymerase inhibitors such as ganciclovir and foscarnet have dramatically reduced the burden of CMV infection in the HCT recipient. However, their use is often limited by toxicities and resistance. Agents with novel mechanisms and favorable toxicity profiles are critically needed. We review recent developments in CMV antivirals and immune-based approaches to mitigating CMV infection.
RECENT FINDINGS
Letermovir, an inhibitor of the CMV terminase complex, was approved in 2017 for primary CMV prophylaxis in adult seropositive allogeneic HCT recipients. Maribavir, an inhibitor of the CMV UL97 kinase, is currently in two phase 3 treatment studies. Adoptive immunotherapy using third-party T cells has proven safe and effective in preliminary studies. Vaccine development continues, with several promising candidates currently under study. No longer limited to DNA polymerase inhibitors, the prevention and treatment of CMV infections in the HCT recipient is a rapidly evolving field which should translate into improvements in CMV-related outcomes.
Topics: Animals; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Cytomegalovirus Vaccines; Drug Resistance, Viral; Foscarnet; Ganciclovir; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Immunosuppressive Agents; Immunotherapy; Immunotherapy, Adoptive; Molecular Targeted Therapy; Opportunistic Infections; Risk Factors; T-Lymphocytes; Treatment Outcome
PubMed: 31981100
DOI: 10.1007/s11899-020-00557-6 -
Computational and Mathematical Methods... 2022In this paper, we proposed and analyzed a realistic compartmental mathematical model on the spread and control of HIV/AIDS-pneumonia coepidemic incorporating pneumonia...
In this paper, we proposed and analyzed a realistic compartmental mathematical model on the spread and control of HIV/AIDS-pneumonia coepidemic incorporating pneumonia vaccination and treatment for both infections at each infection stage in a population. The model exhibits six equilibriums: HIV/AIDS only disease-free, pneumonia only disease-free, HIV/AIDS-pneumonia coepidemic disease-free, HIV/AIDS only endemic, pneumonia only endemic, and HIV/AIDS-pneumonia coepidemic endemic equilibriums. The HIV/AIDS only submodel has a globally asymptotically stable disease-free equilibrium if < 1. Using center manifold theory, we have verified that both the pneumonia only submodel and the HIV/AIDS-pneumonia coepidemic model undergo backward bifurcations whenever < 1 and = max{ , } < 1, respectively. Thus, for pneumonia infection and HIV/AIDS-pneumonia coinfection, the requirement of the basic reproduction numbers to be less than one, even though necessary, may not be sufficient to completely eliminate the disease. Our sensitivity analysis results demonstrate that the pneumonia disease transmission rate and the HIV/AIDS transmission rate play an important role to change the qualitative dynamics of HIV/AIDS and pneumonia coinfection. The pneumonia infection transmission rate gives rises to the possibility of backward bifurcation for HIV/AIDS and pneumonia coinfection if = max{ , } < 1, and hence, the existence of multiple endemic equilibria some of which are stable and others are unstable. Using standard data from different literatures, our results show that the complete HIV/AIDS and pneumonia coinfection model reproduction number is = max{ , } = max{1.386, 9.69 } = 9.69 at = 2 and = 0.2 which shows that the disease spreads throughout the community. Finally, our numerical simulations show that pneumonia vaccination and treatment against disease have the effect of decreasing pneumonia and coepidemic disease expansion and reducing the progression rate of HIV infection to the AIDS stage.
Topics: AIDS-Related Opportunistic Infections; Acquired Immunodeficiency Syndrome; Basic Reproduction Number; Coinfection; Computational Biology; Computer Simulation; Endemic Diseases; Epidemiological Models; HIV Infections; Humans; Models, Biological; Pneumonia; Vaccination
PubMed: 35069778
DOI: 10.1155/2022/3105734 -
Current Opinion in Infectious Diseases Aug 2020In recent years, we have witnessed a remarkable surge in the clinical development of effective biological and cellular therapies for the treatment of neoplastic and... (Review)
Review
PURPOSE OF REVIEW
In recent years, we have witnessed a remarkable surge in the clinical development of effective biological and cellular therapies for the treatment of neoplastic and autoimmune disorders. The present review summarizes our understanding of the pathogen-specific infection risk associated with the use of such therapies.
RECENT FINDINGS
A variety of biologics, in the form of either monoclonal antibodies (Mabs) or small molecule kinase inhibitors (Nibs), are continuously introduced in the clinic for the management of autoimmune and malignant diseases. In addition, cellular therapies such as the infusion of chimeric antigen receptor (CAR) T-cells are becoming increasingly available for patients with treatment-refractory lymphoid malignancies. Some of these biological and cellular interventions exert direct or indirect adverse effects on the induction of protective immune responses against various pathogens, resulting in heightened infection susceptibility.
SUMMARY
The introduction of biological and cellular therapies for the treatment of malignant and autoimmune diseases has been associated with increased infection susceptiblity, which varies greatly depending on the specific immunomodulatory therapy, the infecting pathogen and the recipient patient population. A high index of clinical suspicion and efforts aiming at early diagnosis, targeted vaccination or prophylaxis, and prompt initiation of antimicrobial treatment should help improve infection outcomes.
Topics: Antibodies, Monoclonal; Autoimmune Diseases; Humans; Immunotherapy; Immunotherapy, Adoptive; Infections; Neoplasms; Opportunistic Infections; Protein Kinase Inhibitors; Risk Factors
PubMed: 32657964
DOI: 10.1097/QCO.0000000000000656 -
AIDS Research and Therapy Apr 2024Erythema multiforme (EM) is an immune-mediated mucocutaneous condition characterized by hypersensitivity reactions to antigenic stimuli from infectious agents and... (Review)
Review
Erythema multiforme (EM) is an immune-mediated mucocutaneous condition characterized by hypersensitivity reactions to antigenic stimuli from infectious agents and certain drugs. The most commonly implicated infectious agents associated with EM include herpes simplex virus (HSV) and Mycoplasma pneumoniae. Other infectious diseases reported to trigger EM include human immunodeficiency virus (HIV) infection and several opportunistic infections. However, studies focusing on EM and human immunodeficiency virus (HIV) infection are scarce. even though the incidence of EM among HIV-infected individuals have increased, the direct and indirect mechanisms that predispose HIV-infected individuals to EM are not well understood. In turn, this makes diagnosing and managing EM in HIV-infected individuals an overwhelming task. Individuals with HIV infection are prone to acquiring microorganisms known to trigger EM, such as HSV, Mycobacterium tuberculosis, Treponema pallidum, histoplasmosis, and many other infectious organisms. Although HIV is known to infect CD4 + T cells, it can also directly bind to the epithelial cells of the oral and genital mucosa, leading to a dysregulated response by CD8 + T cells against epithelial cells. HIV infection may also trigger EM directly when CD8 + T cells recognize viral particles on epithelial cells due to the hyperactivation of CD8 + T-cells. The hyperactivation of CD8 + T cells was similar to that observed in drug hypersensitivity reactions. Hence, the relationship between antiretroviral drugs and EM has been well established. This includes the administration of other drugs to HIV-infected individuals to manage opportunistic infections. Thus, multiple triggers may be present simultaneously in HIV-infected individuals. This article highlights the potential direct and indirect role that HIV infection may play in the development of EM and the clinical dilemma that arises in the management of HIV-infected patients with this condition. These patients may require additional medications to manage opportunistic infections, many of which can also trigger hypersensitivity reactions leading to EM.
Topics: Humans; HIV Infections; Erythema Multiforme; Simplexvirus; Opportunistic Infections
PubMed: 38637892
DOI: 10.1186/s12981-024-00607-6 -
Transplant International : Official... Mar 2021Pulmonary infection is a leading cause of morbidity and mortality in renal transplant recipients. In a prospective study, we characterized their epidemiology in a...
Pulmonary infection is a leading cause of morbidity and mortality in renal transplant recipients. In a prospective study, we characterized their epidemiology in a tropical country with high infectious disease burden. Adult renal transplant recipients presenting with pulmonary infections from 2015 to 2017 were evaluated using a specific diagnostic algorithm. 102 pulmonary infections occurred in 88 patients. 32.3% infections presented in the first year, 31.4% between 1 and 5, and 36.3% beyond 5 years after transplantation. Microbiological diagnosis was established in 69.6%, and 102 microorganisms were identified. Bacterial infection (29.4%) was most common followed by tuberculosis (23.5%), fungal (20.6%), Pneumocystis jiroveci (10.8%), viral (8.8%), and nocardial (6.9%) infections. Tuberculosis(TB) and bacterial infections presented throughout the post-transplant period, while Pneumocystis (72.7%), cytomegalovirus (87.5%) and nocardia (85.7%) predominantly presented after >12 months. Fungal infections had a bimodal presentation, between 2 and 6 months (33.3%) and after 12 months (66.7%). Four patients had multi-drug resistant(MDR) TB. In 16.7% cases, plain radiograph was normal and infection was diagnosed by a computed tomography imaging. Mortality due to pulmonary infections was 22.7%. On multivariate Cox regression analysis, use of ATG (HR-2.39, 95% CI: 1.20-4.78, P = 0.013), fungal infection (HR-2.14, 95% CI: 1.19-3.84, P = 0.011) and need for mechanical ventilation (9.68, 95% CI: 1.34-69.82, P = 0.024) were significant predictors of mortality in our patients. To conclude, community-acquired and endemic pulmonary infections predominate with no specific timeline and opportunistic infections usually present late. Nocardiosis and MDR-TB are emerging challenges.
Topics: Adult; Humans; Kidney Transplantation; Nocardia Infections; Opportunistic Infections; Pneumonia; Prospective Studies
PubMed: 33423313
DOI: 10.1111/tri.13817 -
Acta Neurologica Scandinavica Jul 2022Although clinical examinations, neuroimaging, and cerebrospinal fluid analyses are the most important ways to evaluate the impact of HIV infection on the brain and in... (Review)
Review
Although clinical examinations, neuroimaging, and cerebrospinal fluid analyses are the most important ways to evaluate the impact of HIV infection on the brain and in diagnosis of opportunistic infections, several blood biomarkers including HIV RNA concentrations, CD4 +T-cell count, and neurofilament light chain protein (NfL) concentration, along with tests for opportunistic infections can provide important information for clinical decisions.
Topics: Biomarkers; HIV Infections; Humans; Nervous System Diseases; Neurofilament Proteins; Opportunistic Infections
PubMed: 35470863
DOI: 10.1111/ane.13629 -
Mycoses Aug 2020Cryptococcal meningitis remains one of the leading causes of death among HIV-infected adults in the fourth decade of HIV era in sub-Saharan Africa, contributing to... (Review)
Review
Cryptococcal meningitis remains one of the leading causes of death among HIV-infected adults in the fourth decade of HIV era in sub-Saharan Africa, contributing to 10%-20% of global HIV-related deaths. Despite widespread use and early induction of ART among HIV-infected adults, incidence of cryptococcosis remains significant in those with advanced HIV disease. Cryptococcus species that causes fatal infection follows systemic spread from initial environmental acquired infection in lungs to antigenaemia and fungaemia in circulation prior to establishment of often fatal disease, cryptococcal meningitis in the CNS. Cryptococcus person-to-person transmission is uncommon, and deaths related to blood infection without CNS involvement are rare. Keen to the persistent high mortality associated with HIV-cryptococcal meningitis, seizures are common among a third of the patients, altered mental status is frequent, anaemia is prevalent with ensuing brain hypoxia and at autopsy, brain fibrosis and infarction are evident. In addition, fungal burden is 3-to-4-fold higher in those with seizures. And high immune activation together with exacerbated inflammation and elevated PD-1/PD-L immune checkpoint expression is immunomodulated phenotypes elevated in CSF relative to blood. Lastly, though multiple Cryptococcus species cause disease in this setting, observations are mostly generalised to cryptococcal infection/meningitis or regional dominant species (C neoformans or gattii complex) that may limit our understanding of interspecies differences in infection, progression, treatment or recovery outcome. Together, these factors and underlying mechanisms are hypotheses generating for research to find targets to prevent infection or adequate therapy to prevent persistent high mortality with current optimal therapy.
Topics: AIDS-Related Opportunistic Infections; B-Lymphocytes; B7-H1 Antigen; Brain; Cerebrospinal Fluid; Coinfection; Cryptococcosis; Cryptococcus; Cryptococcus gattii; Cryptococcus neoformans; HIV Infections; Humans; Immunity; Incidence; Inflammation; Meningitis, Cryptococcal; Mortality; Prevalence; Programmed Cell Death 1 Receptor; T-Lymphocytes; Treatment Outcome
PubMed: 32472727
DOI: 10.1111/myc.13122 -
BMJ (Clinical Research Ed.) Oct 2019People with immunoreactivity to tuberculosis are thought to have lifelong asymptomatic infection and remain at risk for active tuberculosis. argue that most of these...
People with immunoreactivity to tuberculosis are thought to have lifelong asymptomatic infection and remain at risk for active tuberculosis. argue that most of these people are no longer infected
Topics: AIDS-Related Opportunistic Infections; Antigens, Bacterial; Humans; Immunocompromised Host; Immunosuppression Therapy; Latent Tuberculosis; Mycobacterium tuberculosis; Tissue Transplantation; Tuberculosis; Virus Activation
PubMed: 31649096
DOI: 10.1136/bmj.l5770