Disease In Solid Organ Transplant Recipients Research Articles

Clinical Management and Outcomes of Nontuberculous Mycobacterial Infections in Solid Organ Transplant Recipients: A Multinational Case-control Study.

The management and outcomes of nontuberculous mycobacterial (NTM) infections in solid organ transplant (SOT) recipients are poorly characterized. We aimed to describe the management and 1-y mortality of these patients. Retrospective, multinational, 1:2 matched case-control study included SOT recipients aged 12 y old or older diagnosed with NTM infection between January 1, 2008, and December 31, 2018. Controls were matched on transplanted organs, NTM treatment center, and posttransplant survival at least equal to the time to NTM diagnosis. The primary aim was 1-y mortality after NTM diagnosis. Differences between cases and controls were compared using the log-rank test, and Cox regression models were used to identify factors associated with mortality at 12 mo among cases. In 85 patients and 169 controls, the median age at the time of SOT was 54 y (interquartile range, 40-62 y), 59% were men, and the lungs were the most common site of infection after SOT (57.6%). One-year mortality was significantly higher in cases than in controls (20% versus 3%; P < 0.001), and higher mortality was associated with lung transplantation (hazard ratio 3.27; 95% confidence interval [1.1-9.77]; P = 0.034). Median time (interquartile range) from diagnosis to treatment initiation (20 [4-42] versus 11 [3-21] d) or the reduction of net immunosuppression (36% versus 45%, hazard ratio 1.35 [95% CI, 0.41-4.43], P = 0.618) did not differ between survivors and those who died. NTM disease in SOT recipients is associated with a higher mortality risk, especially among lung transplant recipients. Time to NTM treatment and reduction in net immunosuppression were not associated with mortality.

Clinical Characteristics and Outcomes of Endemic Mycoses After Solid Organ Transplantation: A Comprehensive Review.

Geographically endemic fungi can cause significant disease among solid organ transplant (SOT) recipients. We provide an update on the epidemiology, clinical presentation, and outcomes of 5 endemic mycoses in SOT recipients. Multiple databases were reviewed from inception through May 2023 using key words for endemic fungi (eg, coccidioidomycosis or Coccidioides, histoplasmosis or Histoplasma, etc). We included adult SOT recipients and publications in English or with English translation. Among 16 cohort studies that reported on blastomycosis (n = 3), coccidioidomycosis (n = 5), histoplasmosis (n = 4), and various endemic mycoses (n = 4), the incidence rates varied, as follows: coccidioidomycosis, 1.2%-5.8%; blastomycosis, 0.14%-0.99%; and histoplasmosis, 0.4%-1.1%. There were 204 reports describing 268 unique cases of endemic mycoses, including 172 histoplasmosis, 31 blastomycosis, 34 coccidioidomycosis, 6 paracoccidioidomycosis, and 25 talaromycosis cases. The majority of patients were male (176 of 261 [67.4%]). Transplanted allografts were mostly kidney (192 of 268 [71.6%]), followed by liver (n = 39 [14.6%]), heart (n = 18 [6.7%]), lung (n = 13 [4.9%]), and combined kidney-liver and kidney-pancreas (n = 6 [2.7%]). In all 5 endemic mycoses, most patients presented with fever (162 of 232 [69.8%]) and disseminated disease (179 of 268 [66.8%]). Cytopenias were frequently reported for histoplasmosis (71 of 91 [78.0%]), coccidioidomycosis (8 of 11 [72.7%]) and talaromycosis (7 of 8 [87.5%]). Graft loss was reported in 12 of 136 patients (8.8%). Death from all-causes was reported in 71 of 267 (26.6%); half of the deaths (n = 34 [50%]) were related to the underlying mycoses. Endemic mycoses commonly present with fever, cytopenias and disseminated disease in SOT recipients. There is a relatively high all-cause mortality rate, including many deaths that were attributed to endemic mycoses.

Prevention of Oncogenic Gammaherpesvirinae (EBV and HHV8) Associated Disease in Solid Organ Transplant Recipients.

Long-term risk for malignancy is higher among solid organ transplant (SOT) recipients compared to the general population. Four non-hepatitis viruses have been recognized as oncogenic in SOT recipients-EBV, cause of EBV-associated lymphoproliferative diseases; human herpes virus 8 (HHV8), cause of Kaposi sarcoma, primary effusion lymphoma and multicentric Castleman disease; human papilloma virus, cause of squamous cell skin cancers, and Merkel cell polyomavirus, cause of Merkel cell carcinoma. Two of these viruses (EBV and HHV8) belong to the human herpes virus family. In this review, we will discuss key aspects regarding the clinical presentation, diagnosis, treatment, and prevention of diseases in SOT recipients associated with the two herpesviruses.

Cytomegaloviral Retinitis in a Heart Transplant Patient: Case Report and Review of the Literature

Cytomegalovirus (CMV) poses a significant threat to solid organ transplant recipients (SOTR). The incidence of CMV disease in SOTR varies according to immunosuppressive therapy, antiviral prophylaxis, donor and recipient serologic compatibility, and the transplanted organ: 9% to 23%, 22% to 29% and 8% to 32% after heart, liver and kidney transplant, respectively. CMV retinitis (CMVR) is a rare manifestation of CMV with a high risk of blindness. Infection may vary in severity, from initially clinically silent cases to full-blown advanced changes involving the eye. The most characteristic effects are changes in the retina, which usually begin at the retina's periphery and are asymptomatic, then these changes spread toward the center as the disease progresses and impairs vision. We describe CMV vitritis and retinitis in a 74-year-old patient after heart transplantation conducted in 1992. The first symptom of the disease was low vision in the left eye. Initially no blood viremia was observed; then the CMV viral load in the blood and vitreous body of the right eye was 2454 and 26 million IU/mL.Despite the initiation of treatment (intravitreal and then intravenous ganciclovir), the inflammatory process progressed rapidly and vision in the left eye was lost, although functional visual acuity in the right eye was maintained. Systemic antiviral therapy with intravenous ganciclovir lasted 6 weeks until the eradication of CMV viremia. The patient was on prophylactic therapy with oral valganciclovir for 12 months. A clinically silent course of CMVR delays diagnosis and therapy. Therefore, it is recommended that all SOTR undergo periodic ophthalmologic control to avoid delayed diagnosis.

Defining standards of CARE for invasive fungal diseases in solid organ transplant patients

Fungal infection in solid organ transplant (SOT) recipients is a challenge for physicians. Our aim was to review progress made within the past decade in managing the most important invasive fungal diseases in SOT recipients. Standards of care for candidosis, aspergillosis, mucormycosis and cryptococcosis in this special population are summarized.

Human leukocyte antigen-A genotype as a predictor of cytomegalovirus-pp65 antigenemia and cytomegalovirus disease in solid-organ transplant recipients

BackgroundCytomegalovirus (CMV) infection is one of the most common and severe infections during the post-transplantation period. It threatens the survival of patients and the function of the transplanted organ. Aim of the studyTo screen for CMV infection among solid organ transplantation patients using monitoring of CMV phosphoprotein 65 (CMVpp65) antigenemia and to detect if CMV infection and disease were associated with certain human leukocyte antigen (HLA)-A locus genotypes among the studied group. Subjects and methodsThirty solid organ transplantation patients were included for post-transplantation follow up for symptoms and signs suggestive of CMV disease upto one year. Regular screening for CMV infection was done through CMVpp65 antigenemia detection by the immunofluorescence technique. In addition, HLA-A genotype was determined for all patients using the line probe assay. ResultsThe present study showed that 9 out of 30 patients (30%) were positive for CMVpp65 antigenemia. The detected HLA-A alleles were HLA-A*01(no.=16), HLA-A*02(no.=11), HLA-A*11(no.=5), HLA-A*19(no.=1), HLA-A*24(no.=4), HLA-A*29(no.=1), HLA-A*30(no.=16), HLA-A*92(no.=4). Among the studied cases, 40% showed HLA-A*01–30 type. There was a significant difference (P=0.05) among detected HLA types as regards CMVpp65 antigenemia, with HLA-A*02_11 representing 33.3% of CMVpp65 positive patients and HLA-A*01_30 representing 57.1% of CMVpp65 negative patients. ConclusionCertain HLA alleles may have either a protective or predisposing role in CMV reactivation. Thus, HLA typing might be helpful in estimating the risk of CMV disease during the post-transplantation period and designing individualized therapy as regards the choice between preemptive and prophylactic CMV therapy.

Pneumococcal disease in adult solid organ transplantation recipients

In solid organ transplant (SOT) recipients, Streptococcus pneumoniae can cause substantial morbidity and mortality ranging from non-invasive to invasive diseases, including pneumonia, bacteremia, and meningitis, with a risk of invasive pneumococcal disease 12 times higher than that observed in non-immunocompromised patients. Moreover, pneumococcal infection has been related to graft dysfunction. Several factors have been involved in the risk of pneumococcal disease in SOT recipients, such as type of transplant, time since transplantation, influenza activity, and nasopharyngeal colonization. Pneumococcal vaccination is recommended for all SOT recipients with 23-valent pneumococcal polysaccharides vaccine. Although immunological rate response is appropriate, it is lower than in the rest of the population, decreases with time, and its clinical efficacy is variable. Booster strategy with 7-valent pneumococcal conjugate vaccine has not shown benefit in this population. Despite its relevance, there are few studies focused on invasive pneumococcal disease in SOT recipients. Further studies addressing clinical, microbiological, and epidemiological data of pneumococcal disease in the transplant setting as well as new strategies for improving the protection of SOT recipients are warranted.

Clinical Experience with Immune Monitoring for Cytomegalovirus in Solid-Organ Transplant Recipients.

Novel strategies are needed to further reduce the burden of cytomegalovirus (CMV) disease in solid-organ transplant (SOT) recipients. Measurement of the specific cell-mediated immunity against CMV can identify the actual risk for the development of CMV disease in a given patient. Thus, immune monitoring is an attractive strategy for individualizing the management of CMV after transplantation. A growing number of observational studies on immune monitoring for CMV have been published over recent years, although there is a lack of data coming from interventional trials. In high-risk patients, measurement of CMV-specific T-cell responses appropriately stratifies the risk of CMV disease after discontinuation of antiviral prophylaxis. Immune monitoring may also help to identify patients followed by the preemptive approach at low risk for progression to CMV disease. Pretransplant assessment of cell-mediated immunity in seropositive patients may predict the development of posttransplant CMV infection. Overall, these studies indicate that the use of cell-mediated immunity assays has the potential to improve the management of CMV disease in SOT recipients.

Bartonella henselae‐mediated disease in solid organ transplant recipients: two pediatric cases and a literature review

Bartonella henselae, the etiologic agent of cat-scratch disease, causes a well-defined, self-limited syndrome of fever and regional lymphadenopathy in immunocompetent hosts. In immunocompromised hosts, however, B. henselae can cause severe disseminated disease and pathologic vasoproliferation known as bacillary angiomatosis (BA) or bacillary peliosis. BA was first recognized in patients infected with human immunodeficiency virus. It has become more frequently recognized in solid organ transplant (SOT) recipients, but reports of pediatric cases remain rare. Our review of the literature revealed only one previously reported case of BA in a pediatric SOT recipient. We herein present 2 pediatric cases, one of which is the first reported case of BA in a pediatric cardiac transplant recipient, to our knowledge. In addition, we review and summarize the literature pertaining to all cases of B. henselae-mediated disease in SOT recipients.

Esquemas de prevención de la infección por citomegalovirus: terapia anticipada frente a profilaxis universal

Despite the advances made in the diagnosis and treatment of cytomegalovirus (CMV) infection, this pathogen continues to cause substantial morbidity in solid organ transplant (SOT) recipients. The two main strategies for the prevention of CMV disease are universal prophylaxis and preemptive therapy. Several meta-analyses have found that both strategies are effective in the prevention of CMV disease in SOT recipients compared with placebo, each with its own advantages and disadvantages. Nevertheless, few studies have compared the two approaches to CMV disease in SOT recipients. The present article provides a review of the indications of each of these strategies and the main studies on which they are based.

Valganciclovir to prevent or treat cytomegalovirus disease in organ transplantation

Cytomegalovirus (CMV) is generally considered the most significant pathogen to infect patients following organ transplantation. Significant improvements have been achieved in the management of CMV disease over recent years, especially since the introduction of oral drugs such as oral ganciclovir followed by valganciclovir (VGC), a prodrug of ganciclovir with enhanced bioavailability. Several randomized controlled trials have shown that VGC is an efficacious and convenient oral drug to prevent or treat CMV disease in solid-organ transplant recipients. In this article, we discuss the clinical and pharmacological experience with the use of VGC for the management of CMV in solid-organ transplant recipients. Finally, novel strategies to further reduce the incidence of CMV disease after transplantation are also reviewed.

Prevention of Posttransplant Cytomegalovirus Disease and Related Outcomes with Valganciclovir: A Systematic Review

The precise impact of valganciclovir as preventive therapy for cytomegalovirus (CMV) in solid organ transplant (SOT) recipients is not fully defined. Data from studies using valganciclovir as preemptive therapy or prophylaxis for CMV in SOT recipients were synthesized for descriptive analysis. CMV disease occurred in 2.6% and 9.9% of the patients receiving valganciclovir as preemptive therapy and prophylaxis, respectively. Although the incidence of early-onset (<or=90 days posttransplant) CMV disease was only 0.8% and 1.2% in all patients and R-/D+ patients receiving valganciclovir prophylaxis, the incidence of late-onset (>90 days posttransplant) CMV disease rose up to 8.9% and 17.7% in the prophylactic group, respectively. On the contrary, no patients developed late-onset CMV disease in preemptive group. Both approaches with valganciclovir have successfully decreased CMV disease in SOT recipients. Late-onset CMV disease is a complication observed uniquely with valganciclovir prophylaxis, particularly in R-/D+ patients, but not with preemptive therapy.

Immunocompromised Hosts: Perspectives in the Treatment and Prophylaxis of Cytomegalovirus Disease in Solid‐Organ Transplant Recipients

Cytomegalovirus (CMV) infection is an important complication of solid-organ transplantation. The availability of potent antiviral therapies has decreased the incidence of CMV disease among solid-organ transplant recipients but has also led to challenges, including ganciclovir resistance, late-onset CMV disease, and uncertainty about the optimal duration of prophylaxis or therapy for CMV disease. Specific therapies and management of CMV resistance will be addressed here. The best approach for CMV disease in solid-organ transplant recipients is prevention, but which strategy--prophylaxis or preemptive therapy--is optimal remains debatable. Ganciclovir and valganciclovir remain the best options for prevention and treatment of CMV disease in solid-organ transplant recipients, but they are costly and associated with toxicity. Foscarnet and cidofovir, indicated for the treatment of patients who fail to respond to ganciclovir, are less attractive alternatives because of renal toxicity. Therefore, new therapeutic agents for CMV and an immunogenic, safe CMV vaccine are critically needed.

Cytomegalovirus infection after solid-organ transplantation, its risk factors, direct and indirect effects and prevention strategies

The human cytomegalovirus is widely prevalent among human population and it is the most common viral pathogen that affects both the graft's and solid-organ transplant recipient's survival. The risk is highest in donor-seropositive, recipient-seronegative pairing transplantation. These recipients carry increased risk of developing symptomatic primary CMV infection; however, other risk factors may have an impact on cytomegalovirus activation as well: intensity of immunosuppression, type of organ transplanted, rejection and/or treatment for rejection, HLA-mismatch between recipient and donor, certain HLA-types of the recipient, female sex etc. Cytomegalovirus infection in transplant patients has been associated with both direct (symptoms) and indirect effects which are derived from the immunomodulating impact of the virus such as cellular effects and cytokine expression or systemic immune suppression leading to other opportunistic infections. Prevention of the direct and indirect effects of cytomegalovirus infection is the therapeutic goal in transplanted patients. Most transplant centers use either universal prophylaxis or preemptive therapy to prevent the infection. The advantages and disadvantages of these two preventive strategies and current evidence-based recommendations for preventing cytomegalovirus disease in solid-organ transplant recipients are discussed according to others' and the authors' own observations. According to recommendations of the American and Canadian Societies of Transplantation, most of the centers--after analyzing of the CMV-infection risk factors of the recipients--divide them into three groups: high-, moderate- and low-risk groups. The preventive strategy is attached to the risk-group type. In the high-risk group (R-/D+ and lung transplant patients) the use of the universal prophylaxis is necessary. The patients administered anti-lymphocyte antibodies (ATG, ALG or OKT3) need selective (subtype of universal) prophylaxis. Among the moderate-risk patients (R+/D+ or R+/D-) the doctors may choose either universal prophylaxis or preemptive therapy. Selection of a strategy requires consideration of patient-specific factors as well as practical considerations such as available resources. For avoidance of the indirect effects of CMV infection universal prophylaxis is preferred. The use of preventive proceedings in low-risk patients is the matter of the center's decision.

P711 Legionnaires' disease in solid-organ transplant recipients revisited

P711 Legionnaires' disease in solid-organ transplant recipients revisited

Anti-cytomegalovirus prophylaxis in solid-organ transplant recipients

Ganciclovir and its prodrug, valganciclovir, are more effective than acyclovir in preventing cytomegalovirus (CMV) infection and disease in solid-organ transplant recipients. However, the indirect effects of prophylactic use of ganciclovir and acyclovir are comparable, and the greater effectiveness of ganciclovir may be compensated for by less drug-related toxicity with acyclovir or valacyclovir. No conclusive data exist concerning the best technique and duration of surveillance for CMV infection in patients for whom active surveillance for late-onset CMV should be performed, i.e., those reaching the end of prophylaxis. Only large randomised controlled trials, with long follow-up periods, will provide definitive conclusions regarding the comparative prophylactic roles of the major antiviral agents in this population, and how their use fits with a strategy of active surveillance and pre-emptive therapy.

Cytomegalovirus infection and disease after solid-organ transplantation: Epidemiology, prevention, and therapy

Disease caused by cytomegalovirus (CMV) infection remains one of the largest health concerns in clinical transplantation. CMV (transmitted to recipients before transplantation from exogenous sources, including blood transfusions, or during transplantation through the transmission of dormant virus within the transplanted organ) may replicate subsequent to either primary infection or reactivation. During and subsequent to host immunosuppression. CMV disease often manifests as fever and leukopenia; viral invasion of tissue, with involvement of more than 1 organ, is not uncommon. Formerly, CMV disease was associated with serious morbidity and a substantial decrease in allograft and patient survival rates. Fortunately, thanks to the advent of effective anti viral agent prophylaxis and therapy, CMV disease is lethal rarely today. However, even though the epidemiologic characteristics of disease caused by this viral pathogen have changed over the past 10 to 15 years, it remains a significant cause of morbidity, as shown by rehospitalizations and use of anti viral agent prophylaxis and therapy, which result into increased health care costs. We review current epidemiology, prophylaxis, and therapy of CMV disease in solid-organ transplant recipients.

New Strategies for Prevention and Therapy of Cytomegalovirus Infection and Disease in Solid-Organ Transplant Recipients

In the past three decades since the inception of human organ transplantation, cytomegalovirus (CMV) has gained increasing clinical import because it is a common pathogen in the immunocompromised transplant recipient. Patients may suffer from severe manifestations of this infection along with the threat of potential fatality. Additionally, the dynamic evolution of immunosuppressive and antiviral agents has brought forth changes in the natural history of CMV infection and disease. Transplant physicians now face the daunting task of recognizing and managing the changing spectrum of CMV infection and its consequences in the organ recipient. For the microbiology laboratory, the emphasis has been geared toward the development of more sophisticated detection assays, including methods to detect emerging antiviral resistance. The discovery of novel antiviral chemotherapy is an important theme of clinical research. Investigations have also focused on preventative measures for CMV disease in the solid-organ transplant population. In all, while much has been achieved in the overall management of CMV infection, the current understanding of CMV pathogenesis and therapy still leaves much to be learned before success can be claimed.

New strategies for prevention and therapy of cytomegalovirus infection and disease in solid-organ transplant recipients.

In the past three decades since the inception of human organ transplantation, cytomegalovirus (CMV) has gained increasing clinical import because it is a common pathogen in the immunocompromised transplant recipient. Patients may suffer from severe manifestations of this infection along with the threat of potential fatality. Additionally, the dynamic evolution of immunosuppressive and antiviral agents has brought forth changes in the natural history of CMV infection and disease. Transplant physicians now face the daunting task of recognizing and managing the changing spectrum of CMV infection and its consequences in the organ recipient. For the microbiology laboratory, the emphasis has been geared toward the development of more sophisticated detection assays, including methods to detect emerging antiviral resistance. The discovery of novel antiviral chemotherapy is an important theme of clinical research. Investigations have also focused on preventative measures for CMV disease in the solid-organ transplant population. In all, while much has been achieved in the overall management of CMV infection, the current understanding of CMV pathogenesis and therapy still leaves much to be learned before success can be claimed.

Preemptive and prophylactic ganciclovir therapy for CMV infection in heart transplant patients

Disease caused by cytomegalovirus (CMV) infection remains one of the largest health concerns in clinical transplantation. CMV (transmitted to recipients before transplantation from exogenous sources, including blood transfusions, or during transplantation through the transmission of dormant virus within the transplanted organ) may replicate subsequent to either primary infection or reactivation. During and subsequent to host immunosuppression. CMV disease often manifests as fever and leukopenia; viral invasion of tissue, with involvement of more than 1 organ, is not uncommon. Formerly, CMV disease was associated with serious morbidity and a substantial decrease in allograft and patient survival rates. Fortunately, thanks to the advent of effective anti viral agent prophylaxis and therapy, CMV disease is lethal rarely today. However, even though the epidemiologic characteristics of disease caused by this viral pathogen have changed over the past 10 to 15 years, it remains a significant cause of morbidity, as shown by rehospitalizations and use of anti viral agent prophylaxis and therapy, which result into increased health care costs. We review current epidemiology, prophylaxis, and therapy of CMV disease in solid-organ transplant recipients.